JP2008520585A - Pharmaceutical and therapeutic composition derived from Garcinia mangostana L plant - Google Patents

Abstract

The present invention relates to a pharmaceutical, therapeutic, nutritional, cosmetic, and skin derived from the skin of the mangosteen plant (Garcinia mangostana L.). It relates to scientific compositions and new extraction methods used to produce those compositions. In particular, the present invention, in part, is approximately 0.01% to about 80% xanthone-rich mangosteen pericarp (integument) in new combinations for pharmaceutical, cosmetic, therapeutic or dermatological compositions. With regard to the mixture of extracts, it provides a surprising health benefit. In addition, the invention relates in part to a new extraction method that leads to the production of the new composition of the invention.

Description

[Related applications]
[001] This patent application claims priority to Moffett's US Provisional Patent Application No. 60 / 628,615, filed November 16, 2004.
[Field of the Invention]

[002] The present invention provides a pharmaceutical, therapeutic, nutritional, cosmetic and dermatological composition derived from the pericarp of a Garcinia mangostana L plant. And a new extraction process used to produce a blended extract composition.

[Background of the invention]
[003] The mangosteen tree (Garcinia mangostana L.) is a tropical evergreen tree native to the Malay Peninsula, Myanmar, Thailand, Cambodia, Vietnam, Sunda Islands, and the Moluccas. It is a smooth tree with a low-growing, pyramidal crown, with straight trunks and exfoliating black bark, which contains a yellow, resinous latex. Its leaves are leathery, shiny and oval. The flowers are single female, green, with thick, fleshy and pinkish red edges. Mangosteen fruit is a smooth, spherical berry that matures from a dark reddish to a black-purple color and is usually smooth or brownish Marked with a wound. Each mangosteen fruit usually varies in weight from 75 to 120 grams and usually contains from 2 to 3 well-developed seeds. Mangosteen fruit peel, or rind, contains pectin and tannin, which exudes a thick, firm and bitter yellowish resin. Only about 25-30% of mangosteen fruit consists of edible pulp, with the remainder being hard, bitter pericarp or rind.

  [004] In contrast to the thick outer skin, the edible inner pulp of Mangosteen fruit is widely appreciated for its exquisite flavor. The inner pulp of a single mangosteen fruit usually consists of 4 to 8 fresh, white colored segments. When preparing a white pulp segment for consumption, special care is taken to avoid fouling the pulp segment with resin, tannins and other objects secreted from the peel. The need to separate delicious white pulp from dark purple, dirty, bitter pericarp has long been known to those familiar with mangosteen fruit.

[005] Free radicals (free radicals) are highly reactive species with odd (unpaired) electrons that are produced in the body. There are several (about 5 or 6) endogenous sources of oxidants (oxidants): reduction of molecular oxygen occurs in sequential steps during cellular respiration in the mitochondrion (mitochondrion) and radicals by-product of superoxide (superoxide) 02 ^-, hydroxyl HO, and resulted in a hydrogen peroxide H ₂ O _2; degradation in peroxisomes of fatty acids and other molecules to produce H ₂ O _2; phagocytosis monoxide It causes an oxidative burst of nitrogen (NO), which also reacts with superoxide to produce the oxidizing and nitrifying species of peroxynitrite (ONOO ⁻ ).

  [006] Free radicals are very unstable and react readily with other compounds. Once formed, they can begin a chain reaction of cytotoxicity, which can ultimately lead to cell death. As an example, free radicals and oxidants can trigger lipid peroxidation, lipid peroxidation, and protein and DNA oxidation, causing significant damage to somatic cells. In addition, imbalances in the body of oxidizing species and natural antioxidants lead to oxidative stress, which can be severe, such as the aging process, premature cell death (apoptosis), and skin cancer. It is thought to contribute to the disease.

  [007] Excessive sun exposure contributes to free radical production. The cumulative effects of exposure to ultraviolet radiation (UVA and UVB) are slow to develop, but over time they may present a significant health threat and become life threatening. The effects of ultraviolet light on the skin include several types of sunburn, photosensitivity, immunosuppression, premature aging, and skin cancer, including the following: premalignant lesions Basal cell carcinoma (carcinoma), squamous cell carcinoma, and malignant melanoma. Various other skin diseases are exacerbated or triggered by sun exposure; these include erythematous lupus (surgery), solar urticaria, and polymorphous light eruption. And various immune diseases with cutaneous manifestation.

  [008] Even shorter wavelength UVB light is absorbed by the fragile upper layer of the epidermis causing redness of the skin due to direct damage to keratinocytes, and also leads to subsequent release of inflammatory mediators There is. Longer wavelength UVA penetrates deeper into the skin and is absorbed by melanocytes (melanocytes), elastin, and collagen. UVA contributes relatively little to sunburn erythema, but the damaging effects of UVA on collagen and elastin are manifested as chronic sun-exposed skin premature aging and wrinkling. Collagen and elastin fibers lose their elasticity over time, become thickened and agglomerated, and this eventually leads to skin dermatoheliosis, epidermal thinning, May lead to irregular pigmentation and telangiectasia.

  [009] There are relatively few options for effective protection from UV exposure and the resulting damage it causes. These options include sun (sunlight) avoidance, sun-protection clothing and sunglasses, chemical sunscreens (which operate by absorption of UV light by chemicals), and micronized ) Products containing titanium dioxide or zinc oxide are included. These options may work reasonably well when applied appropriately and consistently, but none of them provides sufficient protection against the oxidative effects of UV damage.

  [010] Antioxidants, such as vitamins A, C, E, and selenium, are chemicals found in whole foods (especially fruits and vegetables) that can eliminate somatic cells from the harmful effects of free radicals. Help protect. Xanthone is also a natural antioxidant, it works at the molecular level, and a rich source of xanthone is found in the fruit pulp of the Garcinia mangostana plant (Garcinia mangostana L). In the area it is originally from, mangosteen plants are put to use by people in various ways. Timber is used for building materials and furniture. The hull or pericarp is used in the tanning and dyeing industries. Fruit pulp is used as a food product. Skin, leaves and bark are raw materials in folk medicine, such as catarrh, cystitis, chronic diarrhea and ulcers, dysentery, eczema, fever, digestive problems, infectious wounds, and mild skin ( Used for mild) illness, ailments). Leaves are used for diarrhea, dysentery, fever, and phlegm in tea and other exudates. Recently, the whole mangosteen plant has been formulated into fruit juice and taken as a health supplement for the prevention of several different maladies.

  [011] Various xanthones have been separated from the mangosteen hull and hull. In particular, two xanthones, alpha- and gamma-mangostin, were separated together with (-)-eepicatechin, procyanidins A-2 and B-2 (Yoshikawa et al., 1994, “Antioxidant constituents from the fruit hulls of mangosteen (Garcinia mangostana L.) originating in Vietnam (Antioxidant constituents from the fruit shells of Garcinia mangostana L.” 114 (2): 129-133: Japanese with English abstract (abstr) .Mangostanol shows strong inhibition of phosphodiesterase of cAMP (Chairungsrilerd and Takeuchi) (Takeuchi) et al., 1996, “Mangostanol, a prenyl xanthone from Garcinia mangostana”, Phytochemistry (phytocytometry). 43 (5): 1099-1102), and gamma-mangosteen show more potent antioxidant activity than BHA (butylated hydroxyanisole, an antioxidant widely used in the food industry) and alpha-tocopherol (vitamin E) (Yoshikawa et al., 1994, mentioned above; and Fan (Fan) and Su (Su), 1997, “Antioxidative mechanism of isolated components from alcohol extract of fruit hulls of Garcinia mongostana L. (Garcinia mongostana L. Antioxidant mechanism of components separated from husk alcohol extract) ”. J Chin Agric Chem Soc (Journal of the Chinese Agricultural Society). 35 (5): 540-551, with English abstract In fact, gamma-mangosteen is a product of cyclooxygenase COX1 and COX2 (Nakatani et al., 2002, “Inhibition of cyclooxygenase and prostaglandin E2 synthesis by α-mangost in, a xanthone derivative in mangosteen, in C6 rat glioma cells (inhibition of cyclooxygenase and prostaglandin E2 synthesis in glioma cells of C6 rats by α-mangosteen, a xanthone derivative in mangosteen) ”, Biochem Pharmacol 63: 73-79, and Nakatani et al., 2004, “g-Mangostin inhibits inhibitor-κB kinase activity and decreases lipopolysaccharide-induced cyclooxygenase-2 gene expression in C6 rat glioma cells. Inhibitor) -κB kinase activity and reduces lipopolysaccharide-induced cyclooxygenase-2 gene expression in glioma cells of C6 rats) ”, Mol Pharmacol. 66 (3): 667-674.) In the creation of prostaglandins from common fatty acids by adding two oxygen molecules to arachidonic acid It is found to directly inhibit the activity of an enzyme that catalyzes the first step, thus initiating a set of reactions that ultimately create a host of free radicals. It was issued. Gamma-mangostin also inhibits DNA topoisomerase (Tosa et al., 1997, “Inhibitory activity of xanthone derivatives isolated from some Guttiferaeous plants against DNA topoisomerases I and II (from some Guttiferaeous plants). Inhibitory activity of isolated xanthone derivatives on DNA topoisomerase I and II) ”, Chem Pharm Bull (Chemical and Pharmaceutical Bulletin). 45 (2): 418-420.) And serotonin receptors Histaminergic and serotonergic receptor-blocking substances from the medicinal plant Garcinia mangostana (Histaminergic and serotonergic receptors from the medicinal plant Garcinia mangostana) -Blocking substances). ”, Planta Med. 62 (5): 471-472 (letter), Chairungsrilerd, Furuk awa, Ohta et al., 1998, “α-Mangostin, a novel type of 5-hydroxytryptamine 2A receptor antagonist”, Naunyn-Schmiedeberg's Arch Pharmacol (Naunin-Schmiedeberg's Achievements of Pharmacolology). 357: 25-31; Chairungsrilerd, Furukawa, Tadao et al., 1998, “Effect of α-mangostin through the inhibition of 5-hydroxy-tryptamine 2A receptors in 5-fluoro- □ -methyltryptamine-induced head-twitch responses of mice (5-hydroxy- □ -methyltryptamine-induced head-twitch responses in mice via inhibition of 5-hydroxy-tryptamine 2A receptor) ) Effect of α-mangostin on the response) ”, Br J Pharmacol. (123 (5): 855-862).

  [012] There is therefore a need for xanthone-rich compositions in pharmacological, therapeutic, cosmetic, dermatological, and sun-protective technologies, which are short- It provides effective protection from systemic oxidative stress caused by period burning, long-period photoaging and photocarcinogenesis, and UV damage. To date, mangosteen hulls have not been developed as a source of xanthone-rich, antioxidant compositions, and no suitable extraction process has been available.

[Summary of Invention]
[013] The described invention provides an anti-oxidant composition, which is a rich source of mangosteen plant, Garcinia mangostana, natural xanthone, but extracted from the pericarp or rind With a highly concentrated xanthone component, it can be applied topically and in an effective manner for the treatment of various human mildness and conditions. Mangosteen plants are also known by various common names and names for different languages in particular. The fruit is covered in the crest by a spear stick (acupuncture) and has a flat remnant of stigma in the rosette at the apex of 4 to 8 triangles, round, dense -From purple to red-purple and smooth externally; 3.4-7.5 cm in diameter. The hull is 6-10 mm thick, red in cross section and purple white inside; it contains bitter yellow latex and purple, contaminated juice. There are 4 to 8 triangular sections of snowy white, fresh, flesh (actually seed seed coats). Fruits can be seedless or have 1 to 5 fully developed seeds, oval-rectangular, somewhat flattened, 2.5 cm long and 1.6 cm wide , It sticks to the body.

  [014] In the course of the inventor's research on natural antioxidants, the inventor found that the extract of pericarp derived from the fruit shell of a mangosteen plant (Garcinia mangostana L.) It has been found that it has the effect of scavenging. In particular, the composition comprises a concentrated extraction product of mangosteen peel, which comprises from about 0.1% to about 80%, in particular between about 0.3% to about 60% of the total weight of the composition mixture. Concentrations, and even more particularly from about 1% to about 40%. In addition, concentrations of about 1%, about 10%, about 20%, and about 40% of specific embodiments are described. Specific examples of these mixtures are shown herein to possess surprising antioxidant properties and are less cytotoxic than previously available crude alcoholic extracts. The medical conditions for which this product is therapeutically useful include sunburn, photosensitivity, immunosuppression, premature aging, psoriasis, several types of skin cancer and various immunological diseases, and inflammation. Included are bacterial or fungal infections, skin rashes, and oxidative stress caused by UV radiation exposure and diet.

  [015] The present invention relates to pharmaceutical, therapeutic, cosmetic and dermatological compositions derived from the pericarp of Garcinia mangostana L plants. The primary objective of the present invention was to provide a pharmaceutical, cosmetic, nutritional, therapeutic and dermatological composition that is rich in natural xanthone, easy to produce and dispense. And by exposure to three classes of ultraviolet (UV) radiation, for example, based on radiation of wavelength, UVA (320-400 nM), UVB (280-320 nM), and UVC (nM less than 280). Opposes the cancerous and aging effects of photo-oxidation caused by benefiting human health. Thus, presented herein is a new composition, which comprises a mixture of about 0.1% to about 80% xanthone-rich concentrate, which is a new extraction process (process) of mangosteen peel / hull Derived from, it has surprising anti-oxidative health benefits. In addition to their strong antioxidant effect, the compositions of the present invention also exhibit strong antiseptic (antiseptic), antibacterial, and antiviral effects, assist and produce and formulate immune responses and wound healing. Easy to do.

  [016] Thereby, in embodiments of the invention, xanthone-rich mangosteen peel extract is present in the composition, between about 0.1% and about 80%, in particular about 0.3% of the total weight of the composition mixture. Present in amounts ranging from% to about 60% and most particularly between about 1% and about 40%; in addition, in certain embodiments, about 1%, 10%, 20%, and Includes 40% composition. Such a composition comprises at least one and generally a number of a plurality of xanthones: (1) calabaxanthone, (2) demethylcarbaxanthone, (3) 6-deoxy-γ- Mangosteen, (4) 1-isomangosteen, (5) 3-isomangosteen, (6) 1-isomangosteen hydrate, (7) 3-mangosteen hydrate (Mahabusarakam etc., 1987), ( 8) Gartanin (Chairungsrilerd et al., 1996), (9) 8-Deoxygartanin (Chairungsrilerd et al., 1996; Govindachari et al., 1971; Sakai et al., 1993), (10) ) Garcinone A (Sen et al., 1982), (11) Garcinone B (Sakai et al., 1993), (12) Garcinone C (Sen et al., 1982), (13) Garcinone D ( Sen et al., 1986), (14) Garcinone E, (15) Mangostanol (prenylxanthone), (16) Mangostanol (polyoxygenated xanthone) ), Α-mangostin (Chairungsrilerd et al., 1996), β-mangostin (Govindachari et al., 1971b; Sakai et al., 1993), γ-mangostin (Chairungsrilerd et al., 1996), (17) 6-deoxy-γ- Mangosteen (Sakai et al., 1993), (18) mangostinone, (19) 1,5-dihydroxy-2- (3-methylbut-2-enyl) -3-methoxyxanthone, 20) 1,7-dihydroxy-2- (3-methylbut-2-enyl) -3-methoxyxanthone (Asai et al., 1995), (21) 1,5-dihydroxy-3-methoxy-2- (3-methylbut-2-enyl) xanthone (Sen et al., 1981), (22) 1,7-dihydroxy-3-methoxy-2- (3-methylbut-2-enyl) xanthone (Mahabusarakam et al., 1987; Sen et al., 1981), (23) 5,9-dihydroxy-2,2-dimethyl-8-methoxy-7- (3-methylbut-2-enyl) -2H, 6H-pyrano [3,2b Xanthen-6-one, (24) 2- (γ, γ-dimethylallyl) -1,7-dihydroxy-3- Toxixanthone (Chairungsrilerd et al., 1996), (25) 2,7-di- (3-methylbut-2-enyl) -1,3,8-trihydroxy-4-methylxanthone, (26) 2,8- Di- (3-methylbut-2-enyl) -7-carboxy-1,3-dihydroxyxanthone (Gopalakrishnan and Balaganesan, 2000), (27) normangostin (ν -Mangosteen) (Govindachari et al., 1971), (28) 1,5,8-trihydroxy-3-methoxy-2- (3-methyl-2-butenyl) xanthone, (29) 1,7-dihydroxy-2 -Isoprenyl-3-methoxyxanthone, (30) xanthone I (Sakai et al., 1993), (31) BR-xanthone A, (32) BR-xanthone B (2,4,5-trihydroxy-1-methoxyxanthone ) (Balasubramanian and Rajagopalan, 1988), (33) Garcinone B, (34) Mangostanol, (35) Mangostenol, (36) Mangostenone A, (37 ) Mangostenone B, α-Mangostin, β-Mangosteen, Mangosteenone, (38) Tovophyllin, and (39) Trapezifolixanthone (Suksamrarn et al., 2002). Compositions comprising such listed ingredients may further comprise any and all active phytochemicals, or combinations thereof, that are present in the hull. Specific examples of about 0.1% to about 80% xanthone-rich extract include at least one of the following xanthones: alpha-, beta-, and gamma-mangosteen, and (-)- Epicatechin, Procyanidins A-2 and B-2, Garcinone A to E, and McRurin or any combination mixture of the above. In other more specific embodiments, the xanthone-rich extract comprises mangosteens; even more particularly, the xanthone-rich extract comprises alpha-, beta or gamma-mangosteen, or a combination thereof.

  [017] The therapeutic efficacy of these compositions can be further enhanced by the addition of varying amounts of other selected pharmaceutical, therapeutic, cosmetic, and dermatological ingredients. (Such a raw material may also be referred to as a “second drug”, see the next fourth object of the present invention). These ingredients include preservatives, treatment agents (such as antimicrobial, anti-fungal, and anti-inflammatory agents), vitamins, flavonoids, solvents, surfactants, emulsifiers (emulsifying properties). Drug), wetting agents, perfumes, and the like.

  [018] A second object of the present invention provides a process for preparing pharmaceutical, therapeutic, nutritional, cosmetic and / or dermatological compositions derived from Garcinia mangostana L. plants. They are abundant in natural xanthones, and it may be useful for the health benefits of mangosteen pericarp / skin, alone or in combination with other supplemental and potentiating components. Bring in one. Thereby, in another embodiment of the present invention, a practical for producing a pharmaceutical, therapeutic, cosmetic and / or dermatological composition derived from the pericarp / husk of a plant of Garcinia mangostana L. And provide economic processing. The treatment leads to a product of xanthone-rich extract, which is between about 0.1% to about 80%, in particular between about 0.3% to about 60%, and even more particularly from about 1% to about 40%. Xanthone between up to%. In some embodiments, about 0.1% to about 80% xanthone-rich extract comprises xanthone from the above list, but more particularly comprises at least one of the following xanthones: alpha- , Beta- or gamma-mangosteen, and (-)-epicatechin, procyanidins A-2 and B-2, or combinations thereof. Even more particularly, xanthone-rich extracts contain mangosteens. Even more particularly, the xanthone-rich extract contains alpha-mangosteen and / or gamma-mangosteen.

  [019] The inventive process for the preparation of these varying compositions utilizes the preparation of highly concentrated and less concentrated extracts, and their formulation or admixing, and ultimately To obtain the desired concentration. Furthermore, tannin is reduced in concentration by these treatments in relation to the initial, naturally occurring relative concentration in xanthone-rich extracts. The tannin concentration can be adjusted independently of the xanthone concentration by pulling away the relative degree of concentration of xanthone and tannin, respectively. By independently adjusting or adjusting the concentration of tannin, the value of tannin antioxidants can be fully exploited (developed), while the undesired potential-cytotoxic effect of tannin is high. It can appear in concentration and can be avoided.

  [020] A third object of the present invention is to provide a method for providing a means of treatment or prevention for skin diseases and conditions resulting from exposure to sunlight, and the diseases etc. Can be mediated by the generation of reactive oxygen species during exposure. A fourth object of the present invention is to provide a therapeutic composition, which combines a xanthone-rich extract of Garcinia mangostana with another second agent to provide a therapeutic or cosmetic treatment for the skin. Can increase the efficiency and profits that each drug provides alone.

[021] The foregoing and other objects, advantages, and features of embodiments of the present invention will become apparent from the following description of illustrative embodiments and in the appended claims. The formulations according to the invention have proven to be particularly useful in the area of pharmaceutical, therapeutic, cosmetic and dermatological compositions, but those skilled in the art (those skilled in the art) It can be appreciated that such formulations and mixtures can be used in a variety of different applications and a variety of different types of manufacture to satisfy a wide variety of pharmaceutical and drug needs. Furthermore, the features and advantages of the invention can be learned by practice of the invention or become apparent to those skilled in the art from reading the description, as will be described hereinafter.
[Brief description of drawings]
It is described in the section (Brief description of the drawings).

[Detailed Description of the Invention]
[035] The present invention relates to pharmaceutical, therapeutic, nutritional, cosmetic and / or dermatological compositions derived from the plants of Garcinia mangostana L. (Mangosteen plants). “Mangosteen” is a term that generally refers to plants, and also has the adjectives “mangosteen peel”, “mangosteen extract”, “mangosteen compound”, or “mangosteen composition” The latter two terms, as used in, refer to plant extracts, compounds produced by plants, and compositions comprising such compounds. The embodiments of the invention described herein provide a uniquely natural compound, generally xanthone, that is extracted from the skin of a Mangosteen plant; even more particularly, approximately 0.1% to about 80% Up to xanthone concentrate is extracted from mangosteen pericarp and is formulated into pharmaceutical, cosmetic, therapeutic or dermatological compositions to benefit human health aspects To disclose. In embodiments of the invention, the xanthone-rich mixture of mangosteen peel extract is between about 0.1% and about 80%, in particular between about 0.3% and about 60%, and even more particularly An amount ranging from about 1% to about 40% of the total weight of the composition mixture. Other specific embodiments include an extract composition of a total weight of about 1%, about 10%, about 20%, and about 40% composition.

  [036] The xanthone-rich extract comprises at least one of the following xanthones: (1) carbaxanthone, (2) demethylcarbaxanthone, (3) 6-deoxy-γ-mangosteen, (4) 1 -Isomangosteen, (5) 3-Isomangosteen, (6) 1-Isomangosteen hydrate, (7) 3-Mangostin hydrate, (8) Gartanine, (9) 8-Deoxygartanine, (10) Garcinone A, (11) Garcinone B, (12) Garcinone C, (13) Garcinone D, (14) Garcinone E, (15) Mangostanol (prenylxanthone), (16) Mangostanol (polyoxygenated xanthone), α -Mangosteen, β-Mangosteen, γ-Mangosteen, (18) Mangostinone, (19) 1,5-dihydroxy-2- (3-methylbut-2-enyl) -3-methoxyxanthone, (20) 1,7-dihydroxy -2- (3-methylbut-2-enyl) -3-methoxyxanthone, (21) 1,5-dihydroxy-3-methoxy-2- (3-methylbutane To-2-enyl) xanthone, (22) 1,7-dihydroxy-3-methoxy-2- (3-methylbut-2-enyl) xanthone, (23) 5,9-dihydroxy-2,2-dimethyl-8 -Methoxy-7- (3-methylbut-2-enyl) -2H, 6H-pyrano [3,2b] xanthen-6-one, (24) 2- (γ, γ-dimethylallyl) -1,7-dihydroxy -3-methoxyxanthone, (25) 2,7-di- (3-methylbut-2-enyl) -1,3,8-trihydroxy-4-methylxanthone, (26) 2,8-di- (3 -Methylbut-2-enyl) -7-carboxy-1,3-dihydroxyxanthone, (27) normangostin (ν-mangostin), (28) 1,5,8-trihydroxy-3-methoxy-2- (3 -Methyl-2-butenyl) xanthone, (29) 1,7-dihydroxy-2-isoprenyl-3-methoxyxanthone, (30) xanthone I, (31) BR-xanthone A, (32) BR-xanthone B (2 , 4,5-trihydroxy-1-methoxyxanthone), (33) garcinone B, (34) mangostanol, (35) mangoste (36) Mangostenone A, (37) Mangostenone B, (38) Tobophilin, and (39) Trapedifolixanthone, and any and all active phytochemicals that exist in the outer skin, or The combination can be included. In certain embodiments of the invention, in the description of more abstract forms, the xanthone-rich extract (from about 0.1% to about 80%) comprises at least one of the following three xanthones: : Alpha-, beta-, and gamma-mangosteen (α-, β-, γ-), in any combination and relative proportion; other specific embodiments further include (-)- Epicatechins, procyanidins A-2 and B-2, garcinone AE, McLurin, and yet other examples may further include any and all active phytochemicals present in the hull, or any A combination mixture of the foregoing compounds can be included. The problems in Garcinia plants with respect to the relatively large number of three forms of mangosteen (α-, β-, γ-) have not yet been established among those who know this field; Are considered to be the most naturally rich and therefore have a greater relative presence in embodiments of the invention. However, neither the present invention nor the claims are bound by this belief, and references to “mangosteen” or “mangosteens” refer to the collective presence of all forms of mangosteen. In addition, other embodiments of the pharmaceutical, therapeutic, cosmetic and / or dermatological compositions include a full range of compounds and compositions that are readily supplied from the plant of Garcinia mangostana It is what is described positively without being restrict | limited to. Accordingly, such embodiments include naturally-supplied compounds that are derived from other plants or organisms, or that are derived from synthetically engineered methods or from genetically engineered organisms. Is included.

[037] The effectiveness of these therapeutic mixtures is further enhanced through the addition of varying amounts of the ingredients of other selected pharmaceutical, therapeutic, cosmetic and dermatological formulations. be able to. Such raw materials include, by way of example, preservatives, treatment agents (such as antimicrobial, anti-fungal, and anti-inflammatory agents), vitamins, flavonoids, solvents, surfactants, emulsifiers, wetting agents. , Fragrances and the like. Furthermore, the description of the so-called second drug will be developed in the next section, the following.
Inclusion of a second active agent in the composition

  [038] The compositions described herein may take a variety of forms, according to embodiments of the invention, and various topical applications, such as lotions, ointments, gels, foams, or It can be used for things like bars and for various moisturizing, cleaning or bactericidal lotions and can contain anti-fungi or bactericidal agents. Typically, the composition of the present invention additionally constitutes a protective, treatment or care milk fat (cream), lotion, gel, foam or soap for the body, especially various For the skin of the body part of the body, including the face, limbs, hands, feet, and for the major anatomical folds of the body and / or mucous membrane (mucous membrane) is there. Thereby, in addition to the components of mangosteen peel extract, these compositions may contain one or more types of other active agents, or second therapeutic agents, various other skins. For the prevention and / or treatment of complaints, conditions, and / or afflictions. “Secondary drug” in this context refers to a therapeutic drug other than that provided with an extract of Garcinia mangostana and, when used in the singular, refers to one or more types of such drugs. It is a general term. In accordance with embodiments of the present invention, particularly with the inclusion of a second agent, unfavorable skin conditions that can be treated include, by way of example only, abnormal cutaneous differentiation, proliferation, or pigmentation, Bacterial infections, parasitic infections, fungal infections, inflammation, pain (pain), or irritation from any source (source), pruritus, viral drugs, epidermis Conditions of deprivation (keratolysis), UV (ultraviolet) radiation damage, seborrhea, dandruff, acne, or acne can be included. Thereby, agents for treating such various adverse skin conditions include dermal differentiation and / or proliferation and / or pigmentation modifiers, antibacterial agents, antiparasitic agents, antibacterial agents Steroidal anti-inflammatory agents, anesthetics, antipruriginous agents, antiviral agents, keratolytic agents, other anti-oxidants, antiseborrheic agents (antiseborrhoeic agents), anti-dandruff agents, and anti-acne agents may be included.

  [039] Examples of these active second agents, summarized below in Table 1, include the following: (1) modify skin differentiation and / or proliferation and / or pigmentation ( modifying), non-exclusive examples include retinoic acid and its isomers, retinol and its esters, vitamins E and D and their derivatives, estrogens such as estradiol, kojic acid or hydroquinone; (2) Antibacterial drugs, non-exclusive examples such as antibiotics from the clindamycin phosphate, erythromycin, or tetracycline family; (3) Antiparasitic drugs, non-exclusive For example, such as metronidazole, crotamiton or pyrethroid; (4) Antibacterial drugs, non-exclusive examples such as econazole, ketoconazole or miconazole or salts thereof Compounds of the dazole family, polyene compounds such as amphotericin B, terbinafine, or alternatively compounds of the allylamine family, such as octopirox; (5) steroidal anti-inflammatory drugs, non- As an exclusive example, such as hydrocortisone, betamethasone valerate or clobetasol propionate, or ibuprofen and its salts, diclofenac and its salts, non-steroidal such as acetylsalicylic acid, acetaminophen, or glycyrrhetinic acid Anti-inflammatory drugs; (6) anesthetics, as non-exclusive examples, such as lidocaine hydrochloride and its derivatives; (7) anti-pruritic drugs, as non-exclusive examples , Such as thenaldine, thenalidine, trimeprazine or cyproheptadine; (8) acyclovir (9) epidermal exfoliating agents, as non-exclusive examples, alpha- and beta-hydroxycarboxylic acids or beta-ketocarboxylic acids, salts, amides or esters thereof, and even more particularly, Hydroxy acids, generally such as glycolic acid, lactic acid, salicylic acid, citric acid and fruit acid, and 5-n-octanoylsalicylic acid; (10) other anti-free radical-drugs or anti- -Oxidizing agents, non-exclusive examples such as alpha-tocopherol or its esters, superoxide dismutase, certain metal-chelating agents or ascorbic acid and its esters; (11) Antifat Leaky drugs, non-exclusive examples such as progesterone; (12) anti-dandruff drugs, non-exclusive examples such as octopirox or zinc pyrithione And (13) anti-acne agents such as retinoic acid or benzoyl peroxide. Further included may be natural-supplied ingredients, which are thought to provide health or ameliorative benefits, such as pomegranate, pomegranite, pomegranate, green tea, ale, beer , Turmeric extracts, seaweed-derived peptides and proteins, and various minerals, both simple and complex.

  [040] For medical conditions or applications where the product is therapeutically effective, conditions resulting from exposure to sunlight, and more particularly from UV radiation of types UVA, UVB, and UVC, and Whatever their source includes disorders more particularly associated with exposure to reactive oxygen species. Embodiments of the therapeutic compositions described herein are understood to be therapeutically effective when they are useful for the prevention of a disease or when they are useful for the treatment of a real disease. Where treatment may include amelioration of symptoms, delay of disease progression, or cure of the disease. Conditions that arise directly or indirectly upon exposure to such radioactive and reactive oxygen species (or that are exacerbated or included as risk factors) are both direct and immediate effects, and for longer periods of time. And the complications and sequelae resulting from direct disability, including longer periods. The embodiments of the present invention are bioprotective, or even more particularly, for example, cardioprotective, because the embodiments work prophylactically or treat a first-stage disease at a very early stage. is there. Embodiments of the present invention are thus bioprotectants, whose bioprotective effects are in particular ways in organs and tissues, for example prevention of cell death or allergy. Or interventions in the treatment of inflammation may reveal whether it is localized or extensive.

  [041] In general, health problems associated with exposure to ultraviolet radiation included skin conditions or illnesses, but more widespread and systemic conditions also occur or such conditions of the skin Or it may be part of a complication that follows as a result of the disease. Thus, such conditions can be summarized as: sunburn, photosensitivity, immunosuppression, premature aging, psoriasis, several types of skin cancer and various immune diseases, and localized or widespread inflammation , Various bacterial or fungal infections, skin rashes, and systemic oxidative stress caused by UV radiation exposure and diet. Actinic keratosis is a precancerous disorder that develops after many years of sun exposure, for example, polymorphic light eruption, polymorphic sunlight. A rash (PMLE) is a rash induced by, for example, sun exposure, which is understood to include the skin-localized allergy and the immune system. Skin cancer types associated with sun exposure include, in order of increasing importance, basal cell carcinoma, squamous cell carcinoma, and malignant melanoma.

[042] Without being bound by theory, the inventor theorizes that UV light impacts the skin through both direct and indirect mechanisms. Direct damage is caused by direct exposure to radiation, and indirect effects include the generation of damaged biological molecules and the generation of highly reactive oxygen species (ROS). Included, and then triggers other biological and pathological processes. Reactive oxygen species can have detrimental effects in the immediate locale, where they occur, as in the skin or at remote sites, where such reactions Species can have a broader systemic effect, such that it can manifest itself in what is called “oxidative stress”. Interventions that effectively reduce the level of reactive species thereby have an anti-oxidant effect, and thus can slow, ameliorate, or stop the progression of a wide range of diseases. In addition, the inventor theorizes that the effectiveness of delivery of anti-oxidant therapeutic agents to cells exposed to reactive oxygen species may be important in the clinical success of the agent. To do. Thereby, aspects of preparation and administration of embodiments of the present invention will now be described.
[Dispensing and management route]

  [043] In accordance with embodiments of the invention, the composition may comprise any pharmaceutical form normally utilized according to the route of administration (eg, topical, infusion, or oral route) and the desired therapeutic effect. To achieve. Easily flowable forms such as solutions and micro-emulsions can also be used, for example, for intralesional injection (for the treatment of various skin illnesses) or for rectal administration, eg inflammatory bowel disease It can be employed for things like Crohn's disease, ulcerative colitis, or the like for the treatment of enemas. However, the composition according to the invention is typically intended for oral or topical application, in particular to the skin.

  [044] Thereby, the compositions represented by embodiments of the present invention can be used in any suitable manner, for example for topical application, eg skin application, eg milk fat, paste, lotion, gel, ointment Poultice, cataplasm, plaster, dermal patch or the like, orally, for example in dosage form (e.g. hard or soft) (In the form of gelatin capsules or tablets), or parenterally. Additionally, the compositions of the present invention can be utilized in the context of advanced topical delivery techniques in conjunction with lipidoid (lipoid) or liposomal techniques, which are self-assembled lipid structures. Lipid structures) are used to control the release rate and depth of active raw material penetration without significant disruption of the skin barrier. Such compositions include, by way of example, phosphatylcholines, ceramides (I, III, and VI), cholesterol, palmitic acid, mevalonic acid, glycerol, and / or 25-hydroxycholecalciferol or any mixture thereof. And can be formulated in a differentiated microcarrier system, which can be self-assembled, and a balanced lipid matrix, especially in the hydro or foam phase As well as in lipid particles or vesicles.

  [045] For topical, oral, and / or parenteral application, the subject compositions of embodiments of the invention may be formulated into any pharmaceutical form commonly employed for such applications. In particular, aqueous, aqueous / alcoholic or oily solutions, lotion or serotype dispersions, anhydrous or lipophilic gels, liquid or semi-liquid consistency emulsions ( Emulsion), e.g. of the milk (milk) type, obtained by dispersion of the fatty phase in the aqueous phase (oil-in-water, o / w) or vice versa (water-in-oil, w / o) or a semi-solid or solid consistency type of milk fat, gel, or foam type, or alternatively a microemulsion, microcapsule, microparticle, or vesicle dispersion ion and / or Or non-ionic types, or even powders, or alternatively, containing propellants under pressure In the form of an aerosol composition. These compositions are formulated according to conventional techniques well known in the art.

  [046] For topical management, the pharmaceutical, cosmetic, therapeutic and / or dermatological compositions of embodiments of the present invention are typically based on unique milk fat (fat fat group). Composition), which is suitable for use alone, as a softener milk fat, or in combination with one or more additional cosmetic or dermatological ingredients. Such additional ingredients include, by way of example only, preservatives, treatment agents, wetting agents, and perfumes. If desired, a fragrancing milk fat that can be applied directly to the wearer's skin using the cosmetic milk fat base composition of the present invention in conjunction with a microencapsulated perfume. Form a composition. Compositions for oral administration can be formulated as drinkable liquids, wafer capsules, gelatin capsules, molasses (syrups), or tablets. By way of example, the subject compositions can be administered in the form of an aqueous, alcoholic or aqueous / alcoholic solution in a suitable surfactant and / or solvent.

  [047] Thereby, when the composition of the present invention is intended for any topical or oral management, various other ingredients are added to the ingredients of the mangosteen extract, The final net weight composition can be finished. By way of example, pharmaceutically acceptable surfactants, solvents, thickening agents (for sustained release), or combinations thereof may also be included. Exemplary solvents include, according to the present invention, lower alcohols, such as ethanol and isopropanol as examples, and most other alkyl alcohols, such as butyl alcohol and propylene glycol, and the like. . Examples of suitable lipophilic surfactants include, by way of example, the transesterification products of natural vegetable oil triglycerides and polyalkylene polyols, which are known in the art. is there. Such oils include transesterification products of various natural (e.g. non-hydrogenated) vegetable oils such as corn (maize) oil, kernel oil, kernel oil, tonsil oil (almond). Oil), edible tuber plant oil, olive oil and palm oil and their mixtures with polyethylene glycol, in particular polyethylene glycol having an average molecular weight of 200 to 800 Daltons. Hydrophilic surfactants, particularly non-ionic hydrophilic surfactants, can also be included. Suitable hydrophilic surfactant components are well known in the art and are any of those previously described herein.

  [048] In particular, the compositions of the present invention comprise a surfactant, or both a surfactant and a solvent (co-solvent) and can be formulated in various ways, as is known in the art. E.g. emulsion, emulsion pre-concentrate (i.e. a composition that provides a regular emulsion in contact with water), o / w or w / o type of micro Emulsions, emulsions of both hydrophilic / lipophilic and lipophilic / hydrophilic types, and other forms such as solutions, suspensions, dispersions, and the like.

  [049] In the case of an emulsion pre-concentrate, something like an o / w emulsion is suitable, particularly where oral administration is contemplated. In the case of preparations, examples include, for drinking or topical application, they include aqueous emulsions of the type o / w or w / o in particular. Exemplary emulsifiers may include, for example, a mixture of glyceryl stearate, polysorbate 60, and / or PEG-6 / PEG-32 / glycol stearate.

  [050] When the composition of the present invention is formulated as an emulsion, the proportion of the fatty phase relative to the total weight of the composition is advantageous for allowing maximum absorption of mangosteen peel extract. A range should be achieved. Thus, the emulsion may also contain various oil and lipid vesicles. The co-emulsifying agents employed in the form of emulsions in oils, emulsifiers and compositions are selected from those conventionally used in the cosmetic and dermatological fields.

  [051] Exemplary oils that are suitable for the compositions of the present invention include mineral oil (mineral oil, liquid petrolatum), plant (vegetable) oil (karate butter and sunflower oil liquid fractions) ), Animal oils (perhydrosqualene), synthetic oils (purcellin oil), silicone oils (cyclomethicone), and fluoro oils (perfluoropolyethers) . Fatty alcohols, fatty acids (stearic acid) and waxes (paraffin wax, Brazilian wax or beeswax) can also be used as fat. When the composition of the present invention comprises an oily gel or solution, the fatty phase can constitute a greater proportion of the total weight of the composition, such as for topical application.

  [052] When the composition of the present invention comprises a liquid softener component in combination with a mangosteen extract component, the liquid softener component typically comprises from about 5 to about 10 weight percent, and more More particularly a percentage by weight percent of about 8. Liquid softener ingredients typically contain C12-15 alcohol benzoate in topical formulations and are non-greasy softeners or softeners that are non-irritating to the eyes and skin Give rise to a combination of drugs. Topical softeners typically give the skin a dry lubricating feel. When the composition of the present invention comprises a solid softener component in combination with a mangosteen extract component, the solid softener component is typically present in a weight percent of about 2 to about 10. When a liquid softener is used in combination with a solid softener, the softener component is typically present in a weight percent up to about 20 weight percent. In one embodiment for topical delivery, the composition according to the invention contains a solid softener in addition to the mangosteen extract component and may also include a wax component as discussed next. . In particular, dialkyl fumarate is a solid softener that gives an elegant, non-greasy feel and is suitable for use as a solid softener. For the purposes of the present invention, dialkyl fumarate and di-C12-15-alkyl fumarate can be considered in particular as waxes, which are usually considered softeners.

  [053] Pharmaceutical, therapeutic, cosmetic and / or dermatological compositions according to the present invention may also be purified or non-purified additives and common in such fields. Auxiliary agents (advantants), which are hydrophilic or lipophilic gelling or active agents, preservatives, flavonoids, additional antioxidants, solvents, perfumes, fillers, sunscreens Such as fungicides, odor absorbers, pigments and colorants. Common natural products such as strawberry, green tea, aloe and turmeric extracts, seaweed-derived peptides and proteins, and minerals may also be included as well. The amounts of these various additives and auxiliaries are those conventionally used under the consideration of the field and range, for example, from 0.01% to 90% of the total weight of the composition. Depending on their particular nature, these additives and auxiliaries may be introduced in the fatty phase, in the aqueous phase and / or in the lipid globules. Exemplary hydrophilic gelling agents that are suitable are carboxy vinyl polymers (carbomers), acrylic copolymers such as acrylate / alkyl acrylate copolymers, polyacrylamide, hydroxypropyl cellulose Such as polysaccharides, natural rubber (gum) and clay (clay), and lipophilic gelling agents, typical examples of which are modified clays such as bentones, stearin Fatty acid metal salts such as aluminum acids and hydrophobic silica (anhydrous silicate), or alternatively ethyl cellulose and polyethylene. Exemplary hydrophilic active agents that can be incorporated include proteins or protein hydrolysates, amino acids, polyols, ureas, allantoins, sugars and sugar derivatives, water-soluble vitamins, starches and plant extracts, especially Aloe vera. ) Extract is included. Exemplary lipophilic active agents include retinol (vitamin A) and its derivatives, tocopherol (vitamin E) and its derivatives, essential fatty acids, ceramides and essential oils.

  [054] Exemplary milk fat or lotion base compositions of the present invention for topical management can include a substantial powder component, which includes a wax component, a volatile component, and / or You may combine the component of a fragrance | flavor. Suitable powder components may be selected from one or more of the following powders: corn starch, oat starch and spherical silicon dioxide. The use of starch is suitable for its appealing, soft texture and smooth finish, and for its ability to absorb or absorb the waxes and fluids of the composition of the present invention. Modified starches that are powders and / or liquids can be further used. However, it is suitable for the starches used in the composition of the invention to be treated so that they do not have a whitening effect when rubbed into the body. In addition, spherical silicone dioxide may be included to enhance the application feel of the starch component to the skin.

  [055] When starch and / or other powders are included in the composition, it is suitably present in the milk fat base composition of the present invention in a weight percent of from about 20 to about 90 of the composition. In aromatic compositions comprising aromatic microcapsules, starch and other powders are typically about 20 to about 60 weight percent of the total weight of the composition, where the weight of the starch component Percentages are typically adjusted, and powdery particulate aromatic microcapsules are adapted when they are present.

  [056] When the wax component is included in a pharmaceutical, therapeutic, cosmetic, and / or dermatological milk fat base composition according to the present invention, one or more of the following waxes: Like ingredients are suitable: ozokerite, myristyl myristate, petrolatum and hydrogenated castor oil. Other waxes also work when there is at least one microcrystalline wax present in the composition of the present invention for stability. Ozocerite and petrolatum are typical microcrystalline waxes for use in the present invention. When a wax is present in a milk fat base composition according to the present invention, it is typically a weight percent from about 10 to about 30 of the total weight of the composition.

  [057] Volatile ingredients can also be included in the cosmetic milk fat base composition to add a silky finish when it is applied to the body. Typically, the volatile component may include cyclomethicone, isoeicosane, or a combination of the two. Other volatile components work in the compositions of the present invention as long as they can be processed without igniting at the temperature required to melt the wax, for example from about 170 to about 180 ° F. Volatile components, if included, are typically present in a weight percent of about 5 to about 20.

  [058] If topical application is anticipated, a thickener may also be included. Suitable thickeners may be those known and employed in the art, examples include pharmaceutically acceptable polymeric materials and inorganic thickeners, for example Are of the following types: polyacrylates and polyacrylate co-polymer resins, eg poly-acrylic acid and poly-acrylic / methacrylic resins; cellulose and cellulose derivatives, alkyl Cellulose, hydroxyalkyl-cellulose, acylated cellulose, and salts thereof, such as sodium-carboxymethylcellulose; polyvinylpyrrolidone, for example, poly-N-inylpyrrolidones and sinylpyrrolidone -Polymers, such as vinylpyrrolidone-vinyl acetate copolymer-; polyvinyl resins, eg polyvinyl acetate And wherein the alcohol, as well as other polymeric materials including gum tragacanth (gum traganth, gum tregacanth), Arabikamugomu (gum arabicum), alginates, example alginic acid and salts thereof, examples are sodium alginate. Inorganic thickeners such as attapulgite, attapulgite, bentonite, and silicates that contain hydrophilic silicon dioxide can also be used.

  [059] The compositions of the present invention can also include one or more types of additional raw materials, as described above, particularly diluents, antioxidants, such as ascorbyl palmitate, butyl Hydroxyanisole (BHA), butylhydroxytoluene (BHT) and tocopherol, examples are α-tocopherol (vitamin E), flavoring agents (purified flavonoids) and others. The use of anti-oxidants, such as tocopherol, in addition to the mangosteen extract component is particularly advantageous. Similarly, if the composition comprises a hydrocolloid thickener, the composition also includes water, thus providing an aqueous micro-emulsion in a gel, paste, milk fat or similar form.

  [060] Further, as mentioned, the pharmaceutical, cosmetic, therapeutic and / or dermatological milk fat composition of the present invention can also include a perfume. Typically, the fragrance comprises either a microencapsulated fragrance or a non-microencapsulated fragrance, or both. When a fragrance is included, it is typically from about 0.01 to about 20 weight percent. While typical microencapsulated fragrances have a powdery consistency, they determine the preferred powder weight percent for the purposes of the present invention. It is not considered as a powder.

  [061] Other optional ingredients can be added to the compositions of the present invention. For example, preservatives, treatment agents (eg, vitamins or ceramides), and wetting agents (eg, lactic acid) can be included in the composition to enhance the appearance or function of the composition. Examples of such additional ingredients suitable for use in accordance with the present invention are known and commercially available.

  [062] In addition, using the combination of ingredients described herein, the subject compositions can also be formulated as a solid preparation that constitutes a soap or a cleaning bar. Injectable compositions can be formulated as aqueous or oily lotions or in the form of serum.

  [063] The amounts of the various components of the composition according to the invention are those conventionally used and considered in the art, and according to the intentions in the various compositions, means well known in the art and Can be formulated in combination. Prophylactic, therapeutic and / or cosmetic and dermatological treatments according to the present invention are carried out, and cosmetic or hygienic compositions are applied to the skin of the body, especially for topical use. By applying these compositions according to conventional techniques for administering them. For example: application to the skin, scalp and / or mucous membranes for milk fat, gel, serum and lotion.

[064] However, prophylactic, therapeutic, and / or cosmetic and dermatological compositions according to the present invention are typically formulated as detailed above, but the compositions of the present invention are also Can be delivered in any form known in the art, such as tablets, capsules, dispersions, solutions, suspensions, other transdermal delivery systems, lipophilic patches, soaps Or something like a deodorant. If the mangosteen peel extract mixture is supplemented with juice concentrate, then the liquid drink is a convenient delivery form, but other delivery forms are equally effective, and simply Requires the use of powders, excipients, auxiliaries, or other equivalent forms of carriers. Tablet or capsule forms of the composition can be prepared and coated by methods known to those skilled in the art. The potency of this xanthone-rich mixture of mangosteen peel extract is also enhanced through the addition of other raw materials, which are believed to react synergistically with natural xanthone compounds.
[Processes for the production of pharmaceutical, therapeutic, nutritional, cosmetic and / or dermatological compositions from mangosteen peel peel extracts]

  [065] An object of the present invention is to provide a process for preparing pharmaceutical, therapeutic, cosmetic and / or dermatological compositions derived from Garcinia mangostana L. plants, which is a natural xanthone. Abundant in this way, and thus the holistic benefits of mangosteen peel / husk, either alone or with other supplemental and enhancing components, such as flavonoids and / or tannins, or With other “second” therapeutic agents. Thus, in another aspect of the present invention, Garcinia mangostana L. Economical for producing pharmaceutical, therapeutic, cosmetic and / or dermatological compositions derived from plant pericarp extracts Presents the correct processing.

  [066] The present invention relates in particular to a new processing method for the extraction of xanthone-rich extract products from the mangosteen plant peel / husk, which is the ultimate pharmaceutical, therapeutic, cosmetic From about 0.1% to about 80% of the weight component of the top and / or dermatological composition. Typically, about 0.1% to about 80% xanthone-rich extract comprises at least one of the following xanthones: alpha- and gamma-mangosteen, and (−)-epicatechin, procyanidin A-2 And B-2, or combinations thereof. Even more particularly, xanthone-rich extracts comprise mangosteens. Even more particularly, the xanthone-rich extract comprises alpha- or gamma-mangosteen, or a combination of both.

  [067] Tannins are an important component of mangosteen extracts and vary with respect to their biological effects depending on the dose and method of administration. At high doses, tannins can be toxic because of their ability to interact with proteins and chelate metals. However, tannins are also potent antioxidants and this property can be exploited when they are administered at a suitable dose level. It is therefore important that the level of xanthone is concentrated during the extraction and processing steps in embodiments of the invention and separated from the directly proportional variation in tannin concentration. Thus, the inventive example of treatment provides independent handling or adjustment of the tannin concentration in the peel extract, making it suitable for the final concentration of xanthone and for the intended use of the composition. Such modulation provides a composition that is optimized for low cytotoxicity (cytotoxicity) and high antioxidant properties. Demonstration of such properties is provided in the following example section, which is an in vitro study of oxygen radical absorption capacity (ORAC) cytotoxicity and bench (lab bench) of compositions that are embodiments of the present invention. Oriented for testing.

  [068] The extraction methods disclosed herein result in a greater proportion fractionation and elimination of the portion of tannin from certain embodiments with pericarp / skin xanthone extract present at about 40%. The concentration of tannin in certain embodiments in which the extract is present at about 1% has no tannin that decreases relatively in this manner, and in some embodiments, mangosteen present at 10% and about 20%. Such as those with xanthones, the tannin concentration can be increased by the treatment process, increasing the ORAC value (see next treatment example). Cytotoxicity investigations were performed here for the various extracted end products obtained by these methods, and the reduced cytotoxicity is the final for topical use at various concentrations of pericarp extracts. Various other extraction processes have been demonstrated in a typical composition, compared to not reducing the relative tannin portion of the peel rind extract.

  [069] The extraction process described next herein results in a dominant mangosteen peel extract product, which can be added to various other ingredients to formulate the composition, which The extraction product is comprised in a single pharmaceutical, cosmetic, therapeutic or dermatological composition at a final concentration of about 0.1% to about 80%. In particular, in embodiments of the present invention, the extraction process may comprise a mixture of mangosteen peel extract product from between 0.1% to about 80% of the total weight of the composition mixture, even more particularly about 0.3%. In the amount of concentrations ranging from% to about 60%, and even more particularly from about 1% to about 40%. Typically, the fruit rind of Garcinia mangostana (“mangosteen”) consists of three major chemical components: (1) mangosteen, (2) flavonoids, and (3) tannins. The processes described below are useful for producing the three major chemical components in different ratios, and are particularly useful for the production of the three specific embodiments of the present invention: (1) Water-soluble mangosteen hull extract with about 1% mangosteen, (2) mangosteen hull extract with about 10% mangosteen, (3) mangosteen hull extract with about 20% mangosteen, and (4) about 40 Mangosteen skin extract with% mangosteen.

[070] Thus, a typical extraction process according to the present invention is a two-step process. The first step involves water extraction and the second step involves alcohol extraction. The end result is a mangosteen rind extract where either up or down regulation of tannin levels is possible with respect to the relative xanthone presence level, if desired. Both water and alcohol extraction steps according to the present invention can include several auxiliary (sub) steps. Although various amounts and volumes are subsequently demarcated herein, various other amounts, volumes, and comparable components may be substituted and / or added without departing from the spirit of the invention. Or it can be deleted. There are two specific methods, but they can be practiced to correlate with each other to obtain the preceding three compositions or product-defined examples.
[Two methods to obtain three compositions]
[Method A]

  [071] The first method (Method A) comprises 3 to 4 separation processes, each with several (several, 5 or 6) auxiliary (sub) -steps. The first treatment (Figure 1) involves water extraction, the second treatment involves alcohol extraction (Figure 2), the third treatment involves additional water extraction (Figure 3), which is an additional It can be followed by a fourth enrichment process (Figure 4). The end result is a mangosteen rind extract rich in mangosteen. Both water and alcohol extraction processes include several sub-steps described below in accordance with the present invention. Various quantities and volumes are then partitioned herein, but various other quantities, volumes, and comparable components may be substituted and / or added without departing from the spirit of the invention, or It is understood that it can be deleted.

  [072] In Method A, the hull is first extracted with water, and then the spent rind is then extracted with an organic solvent and again with water. Preferably, the first water extraction treatment includes the following steps. First, a known amount of dried, purified mangosteen pieces is loaded in a suitable extractor with about 6 volumes of demineralized water (DM water). The reactor is then heated by passing steam through an external jacket to about 85 ° C. and the temperature is maintained under circulation for up to about 2 hours. After about 2 hours, the heating is stopped and the temperature is cooled to room temperature. The water extract is then screened into a cleaned stainless steel container to give water extract # 1.

  [073] Second, load 4 volumes of DM water into the extractor. The reactor is then heated to about 85 ° C. by passing steam through an external jacket, and the temperature is maintained under circulation for up to 2 hours. After about 2 hours, heating is stopped, the temperature is cooled to room temperature, and the water extract is screened into a cleaned stainless steel container to give water extract # 2. Combine both water extracts (1 and 2) and concentrate to a total solids of 20-25%. This water extract is named Extract-A, which is part of product #I.

[074] The chemical composition of the product is as follows:

  [075] In Method A, the organic solvent extraction process occurs after the water extraction process and includes the following steps. First, a known quantity of re-dried mangosteen hull from the water extraction process is loaded with about 6 volumes of 80% alcohol into a suitable extractor. The extractor is then heated to 65 ° C.-75 ° C. by passing steam through an external jacket, and the temperature is maintained at the reflux conditions of the extraction solvent and continued under circulation for up to about 2 hours. After about 2 hours, the heating is stopped and the temperature is cooled to room temperature. Sift the alcohol extract into a cleaned stainless steel container: give solvent extract # 1.

  [076] Second, 4 volumes of 80% alcohol are loaded into the extractor. The extractor is then heated to reflux temperature by passing the steam through an external jacket, and reflux is continued under circulation for about 2 hours. After about 2 hours, the heating is stopped and the temperature is cooled to room temperature. The extract is then sieved into a cleaned stainless steel container: Solvent extract # 2 is provided. This process can be repeated three times to give solvent extract # 3. All solvent extracts are combined and loaded into a suitable reactor.

  [077] Third, the solvent from the extract is distilled and concentrated to a semi-solid paste containing 40-45% total solids (TS). The semi-solid paste is kept for sedimentation at room temperature for 8-10 hours. After deposition, the paste is divided into two parts, an upper layer and a lower (lower) layer. The top layer is separated and sieved through an approximately 5-micron (μm) filter. The residue after sieving of the lower and upper layers is mixed to give a wet cake. The wet cake is then dried at about 75-80 ° C. under constant vacuum and crushed: to give Extract-B. This product is part of product #II.

  [078] Fourth, concentrate the screened top layer to a paste of 20-25% total solids. This product is highly water soluble and is added into Extract-A, which is part of product #I.

  [079] In Method A, preferably, after the organic solvent extraction treatment, a second water extraction treatment takes place to obtain another tannin. This process includes the following steps. First, a known amount of dried product is loaded into a suitable extractor with about 4 volumes of DM water. The extractor is heated to about 85 ° C. by passing steam through the outer jacket. The temperature is maintained under circulation for up to about 2 hours. After about 2 hours, the heating is stopped and the temperature is cooled to room temperature. Sifting the water extract into a cleaned stainless steel container: give water extract # 3.

  [080] Again, 4 volumes of DM water are loaded into the extractor and heated by passing steam through the outer jacket to about 85 ° C. Maintain temperature under circulation for up to about 2 hours. After 2 hours, the heating is stopped and the temperature is cooled to room temperature. Sifting the water extract into a cleaned stainless steel container: give water extract # 4. Combine both extracts (3 and 4) and concentrate to a total solids of 20-25%. This water extract is added into Extract-A, which is part of product #I.

[081] At this point, mangosteen can be enriched from about 20% to> 40%. In this treatment, the wet cake of Extract-B is treated again to give an extract containing> 40% γ-mangosteen, which is part of product #III. First, a known amount of extract (wet cake) containing about 20% mangosteen is loaded with about 8 volumes of DM water in a suitable reactor and stirred well for about 30 minutes. Steam is passed through the reactor jacket and the reaction mass is heated to about 75-80 ° C. with constant agitation for about 1 hour. The reaction mass is then cooled to room temperature by withdrawing from a steam jacket and unloaded in a cleaned stainless steel container and kept at room temperature for about 10-12 hours. The top layer is then tilted and the bottom sediment mass (wet cake) is collected. The deposited mass is then sieved through an approximately 5-micron mesh and the wet cake is collected. DM water is added to the wet cake to make it into a slurry. Again, the mass is sieved through an approximately 5-micron mesh to remove tannin from the product. Repeat this washings more than about 2 times. The wet cake is then dried at about 75-80 ° C. under reduced pressure and crushed: to give Extract-C. This product is part of product #III. All three water washings and screened top layers are combined and loaded into the reactor and concentrated to a 20-25% total solids paste. This water extract is added into Extract-A, which is part of product #I.
[Method B]

  [082] The second method (Method B) comprises three separate processes, each with several auxiliary steps. The first treatment involves the extraction of the hull with an organic solvent (Figure 5), the second treatment involves the extraction of the use with water (Figure 6), and the third treatment is an additional enrichment. Includes processing (Figure 7). The end result is a mangosteen rind extract with an even greater proportion of mangosteen. Various quantities and volumes are then partitioned herein, but various other quantities, volumes, and comparable components may be substituted and / or added without departing from the spirit of the invention, or It is understood that it can be deleted.

  [083] In the first treatment of Method B (FIG. 5), the skin is first extracted with an organic solvent and then with water. First, a known amount of dried and purified mangosteen hull is loaded into a suitable extractor with about 6 volumes of 80% alcohol. The reactor is then heated to about 65 ° C.-75 ° C. by passing steam through an outer jacket, maintaining the temperature at the reflux conditions of the extraction solvent, and continuing under circulation for up to about 2 hours. After about 2 hours, the heating is stopped and the temperature is cooled to room temperature. The alcohol extract is then sieved and stored in a cleaned stainless steel container to give solvent extract B # 1.

  [084] Approximately 4 volumes of 80% alcohol is then loaded into the extractor and heated by passing steam through the outer jacket. Heating is brought to reflux temperature and reflux is continued under circulation for up to about 2 hours. After about 2 hours, the heating is stopped and the temperature is cooled to room temperature. The extract is then screened and stored in a cleaned stainless steel container to give the solvent extract B # 2. Repeat these steps one more time and collect the extract: to give solvent extract B # 3.

  [085] All three solvent extracts are combined and loaded into a suitable reactor. The solvent is distilled and the extract is concentrated to a semi-solid paste containing about 40-50% total solids, which is kept for about 10 hours, and then sieved through a 5-micron filter. The wet cake is then dried in vacuo at about 75-80 ° C. and crushed: to give extract-B. Combine both Method A extract-B and Method B extract-B, and this product is part of product #II. The final product is a light brown powder, and its chemical components are as follows:

  [086] Concentrate the filtered top layer to a paste of 20-25% total solids. This product is highly water soluble, and it is added into Extract-A, which is part of product # 1. Product #I may be added to Product II and the content of γ-mangostin, flavonoids and tannins is equilibrated to give the finished product II as described in the table above. Filtrate is added into Method A Extract-A, which is a water-soluble product, and it is included in Product #I.

  [087] The second treatment of Method B (Figure 6) involves the extraction of the use with water. First, a known amount of dry use from the first treatment of Method B (B.1) is loaded with about 6 volumes of DM water in a suitable extractor and steam is externalized to about 85 ° C. Heat by passing through a jacket. The temperature is then maintained under circulation for up to about 2 hours. After 2 hours, the heating is stopped and the temperature is cooled to room temperature. Sifting the water extract into a cleaned stainless steel container: give the water extract B # 1.

  [088] About 4 volumes of DM water is then charged into the reactor and heated by passing steam through an outer jacket to about 85 ° C. Maintain temperature under circulation for up to about 2 hours. After 2 hours, the heating is stopped and the temperature is cooled to room temperature. Sift the water extract into a cleaned stainless steel container: give water extract B # 2. Repeat these steps once more and collect the extract: to give the water extract B # 3.

  [089] Combine all three water extracts and load it into a suitable reactor. The water in the extract is then distilled and the extract is concentrated to 20-25% total solids (TS). The extract is then added to the water extract-A of Method A, which is part of product #I.

  [090] The third treatment of Method B (FIG. 7) is for enrichment of the extract comprising from about 20% mangosteen to about> 40%. For this purpose, the wet cake obtained during the first treatment of method B (B.1) is further washed with water. A known quantity of extract containing 20% γ-mangostin is loaded with about 8 volumes of DM water in a suitable reactor and stirred well for 30 minutes. Steam is passed through the reactor jacket and the reaction mass is heated to about 75-80 ° C. for about 1 hour under constant agitation. The reaction mass is then cooled to room temperature by recovery of steam from the jacket, unloaded in a cleaned stainless steel container, and kept at room temperature for about 10-12 hours. The top layer is then tilted and the bottom sediment mass is collected. The sediment mass is then sieved through a 5-micron filter and the wet cake is collected. DM water is added to the wet cake and brought to a slurry, which is again sieved through a 5-micron mesh to remove tannins from the product. Repeat washing more than twice. The wet cake is then dried at about 75-80 ° C. under reduced pressure and pulverized: to give Method B Extract-C.

  [091] Combine Extract-C of both Method A (A.4) and Extract-C of Method B (B.3) and use this product for the production of Product #III. The chemical components of the product are as follows:

  [092] To add product- # I and / or product- # II to product #III to give the finished product III as described in Table A above, γ-mangostin, flavonoids, and Tannin content can be equilibrated.

  [093] All three water wash and screened top layers are then combined, loaded into the reactor and concentrated to a paste of about 20-25% total solids. This is then added into Extract-A, which is a part of Product #I. Extract-A (consisting of all water-soluble portions of different extracts) is then spray dried. The variables for spray drying are as follows: a) inlet temperature at about 250 ° C., b) outlet temperature at about 108 ° C., and c) chamber (chamber) pressure about 5 mm in the water column. The different extracts produced from the above methods A and B are combined in this manner to obtain three desired products, namely products #I, #II and #III; such appropriately standardized embodiments Examples are outlined in the following table:

[094] Two different methods are developed to develop mangosteen extracts containing 40% gamma-mangosteen. Method 1 includes extracting the hull with DM water and then extracting the use with an organic solvent. Method 2 involves extracting the hull directly with an organic solvent and then washing the concentrated extract with DM water.
[Method 1 (for 40% mangosteen)]

  [095] Method 1 comprises the following steps: After extracting a piece of mangosteen rind with DM water (as in Method A treatment # 1 above), the residual water from the use is completely drained. The remaining moist mangosteen hull pieces are known as hull use. A known amount of hull use is then loaded with about 6 volumes of 90% organic solvent, ie alcohol, in a suitable extractor. The extractor is then heated to about 65 ° C.-75 ° C. by passing steam through the outer jacket, and the temperature is maintained at the reflux conditions of the extraction solvent and continued for up to about 2 hours. After 2 hours, the heating is stopped and the temperature is cooled to room temperature. The alcohol extract is then sieved into a well-purified stainless steel container: giving solvent extract # 1.

  [096] Approximately 4 volumes of 80% alcohol is then loaded into the extractor and heated by passing steam through an outer jacket to reflux temperature. Continue heating and refluxing for up to about 2 hours. After 2 hours, the heating is stopped and the temperature is cooled to room temperature. The extract is then sieved into a well-purified stainless steel container: giving solvent extract # 2. Repeat these steps and collect the extract: give solvent extract # 3. All three solvent extracts are combined and collected in a suitable reactor. The solvent is distilled off from the extract and concentrated to a semi-solid paste containing about 40-45% total solids (TS). The chemical composition of the concentrated extract is as follows:

  [097] The concentrated paste is then held for deposition for about 10-12 hours at room temperature. After deposition, the paste is divided into upper and lower layers. Both layers are separated and analyzed, and the results continue as follows:

  [098] The bottom layer is separated and sieved through an approximately 5-micron filter. A minimum amount of water is added to bring it to a slurry, and it is sieved through an approximately 5-micron filter, and the wet cake is sucked dry at about 80 ° C. under constant vacuum. ). The final product is a light brown powder; the chemical composition of the final product is as follows:

  [099] Method 2: A semi-solid product was obtained from processing of mangosteen husk extract containing 20% γ-mangosteen (TDS 20-25%), which was also added to about 40% of γ-mangosteen and above Can be used for enrichment of extracts containing up to. Thereby, about 20% to about 40% and above is achieved by two different treatments for further enrichment of γ-mangostin.

  [0100] In treatment # 1: Load a known quantity of extract containing about 20% γ-mangosteen with about 5 volumes of DM water in a suitable reactor and stir well for 30 minutes. A volume of about 50 L of 5% potassium hydroxide (KOH) is prepared by dissolving 2.5 kg KOH in 50 L DM water. This 5% KOH solution is slowly added to the reaction mass under constant agitation to bring the pH in the range of about 8.0 to about 8.2. The reaction mass is heated to about 55-60 ° C. under constant stirring for about 1 hour. The reaction mass is then cooled to room temperature and the pH is checked and maintained by adding 5% KOH from about pH 8.0 to about 8.2. Again the reaction mass is heated to about 55-60 ° C. for about 30 minutes with constant stirring. The reaction mass is then lowered to room temperature, deloaded in a cleaned container and kept at room temperature for about 10-12 hours. The top layer is then tilted and the bottom sediment mass is collected. Sift the deposited mass through an approximately 5-micron filter and collect the wet cake. A minimum amount of DM water is added to the wet cake, it is brought to slurry, and again it is sieved through an approximately 5-micron mesh to remove excess KOH from the product. The wet cake is then dried at about 75 ° C. under reduced pressure.

  [0101] In treatment # 2, a known amount of extract containing 20% γ-mangosteen is loaded with about 8 volumes of DM water in a suitable reactor and stirred well for about 30 minutes. Steam is passed through the reactor jacket and the reaction mass is heated to about 75-80 ° C. for about 1 hour under constant agitation. The reaction mass is then cooled to room temperature by recovery of steam from the jacket. Pass the brine solution through the jacket and cool (chill) the reaction mass to about -5 ° C for about 5 hours. The temperature of the reaction mass is then brought to room temperature. The load is reduced in a stainless steel container that has been cleaned of the reaction mass and it is kept at room temperature for about 10-12 hours. Distill the top layer and collect the bottom sediment mass. The deposited mass is then sieved through an approximately 5-micron mesh and the wet cake is collected. Add DM water to the wet cake to make it into a slurry. Again, it is sieved through an approximately 5-micron mesh to remove tannins from the product. The water wash is then repeated more than twice and the wet cake is then dried at about 75 ° C. under reduced pressure and ground. The chemical composition of the extract is as follows:

  [0102] All three washings are then combined, loaded into the reactor, concentrated to a 20-25% TS paste, and the product is spray dried. The variables for spray drying are: (a) Inlet temperature: about 250 ° C, (b) Outlet temperature: about 108 ° C, and (c) Chamber pressure: about -5. (Mm in water column) ).

  [0103] This water product is water soluble and can be used as a diluent for mangosteen rind extract to prepare a formulation comprising the desired amount of γ-mangosteen. The final product is a brown powder. This product is referred to as “product (a)” and the same is added in desired amount to product I above. The chemical composition of the product is as follows:

[Examples of production processing and in vitro and bench-level studies]
[Processing example]
[Process A.1: Extraction of mangosteen skin with water]
[0104] Method-A: In Method-A, as depicted in FIG. 1 and as follows, the hull is first extracted with water and then the product is then extracted with an organic solvent and again with water:
1. Loading a known amount of dried and purified mangosteen skin pieces in a suitable extractor.
2. Loading 6 volumes of desalted water (DM water).
3. Start heating the extractor by passing steam through the outer jacket.
4. Heating to 85 ° C and maintaining the temperature under circulation for up to 2 hours.
5. Stopping heat input after 2 hours and cooling to room temperature.
6. Sifting the water extract into a purified stainless steel container (water extract # 1).
7. The process of loading 4 volumes of DM water into the extractor.
8. Starting the heating of the reactor (extractor) by passing steam through the outer jacket.
9. Heating to 85 ° C and maintaining the temperature under circulation for up to 2 hours.
10. Stop heat input after 2 hours and cool to room temperature.
11. Screening the water extract into a purified stainless steel container (water extract # 2)
12. Combine both water extracts and concentrate to 20-25% total solids. This water extract is named Extract-A, which is part of product #I. The chemical composition of the product is as follows:

[0105] Process A.2, as depicted in Figure 2, and operates as follows:
1. Loading a known amount of re-dried use of mangosteen rind from treatment A.1 into a suitable extractor.
2. The process of loading 6 volumes of 80% alcohol, ie alcohol.
3. Initiating the heating of the reactor by passing steam through the outer jacket.
4. Heating to 65 ° C-75 ° C and maintaining the temperature at reflux conditions of the extraction solvent and continuing under circulation for up to 2 hours.
5. Stop heating after 2 hours and cool to room temperature.
6. Sifting the alcohol extract into a purified stainless steel container (solvent extract # 1).
7. The process of loading 4 volumes of 80% alcohol into the reactor.
8. Initiating heating of the reactor by passing steam through the outer jacket.
9. Heating to reflux temperature and continuing reflux under circulation for up to 2 hours.
10. Stop heat input after 2 hours and cool to room temperature.
11. Sieving the extract into a purified stainless steel container (solvent extract # 2).
12. Repeat steps 7 to 11 and collect the extract (solvent extract # 3).
13. Combining and loading all three solvent extracts into a suitable reactor.
14. Evaporate the solvent from the extract and concentrate to a semi-solid paste containing 40-45% total solids.
15. Retaining semi-solid paste for deposition for 8-10 hours at room temperature.
16. The process of separating the paste into two parts, upper and lower layers, after deposition
17. Separating the bottom layer and sieving through a 5-micron filter.
18. Mixing the bottom layer and top layer residue after sieving to give a wet cake.
19. Drying the wet cake under constant vacuum at 75-80 ° C. and grinding it (extract-B) (this product is part of product #II).
20. Concentrate the screened top layer to a paste of 20-25% total solids (this product is highly water soluble and added into Extract-A, which Part of product #I).
[Process A.3: Extraction of used materials with water]

[0106] In this treatment, as shown in FIG. 3, the used product after solvent extraction is extracted once more with water to obtain other tannins.
1. The process of loading a known amount of dry use into a suitable extractor.
2. The process of loading 4 volumes of DM water.
3. Initiating the heating of the reactor by passing steam through the outer jacket.
4. Heating to 85 ° C and maintaining the temperature under circulation for up to 2 hours.
5. Stopping heat input after 2 hours and cooling to room temperature.
6. Sifting the water extract into a purified stainless steel container (water extract # 1).
7. Loading 4 volumes of DM water into the reactor
8. Initiating heating of the reactor by passing steam through the outer jacket.
9. Heating to 85 ° C and maintaining the temperature under circulation for up to 2 hours.
10. Stop heat input after 2 hours and cool to room temperature.
11. Screening the water extract into a purified stainless steel container (water extract # 2).
12. Combine both extracts and concentrate to 20-25% total solids (add this aqueous extract into Extract A of Process A.1, which is the product #I Is one part of).
[Process A.4: Mangosteen enrichment from 20% to> 40%]

[0107] In this treatment (see Figure 4), the wet cake of Extract-B from treatment A.2 was treated again to give an extract containing> 40% γ-mangosteen, which was product #III Is one part.
1. Loading a known quantity of an extract (wet cake) containing 20% γ-mangosteen in a reactor.
2. Adding 8 volumes of DM water into the reactor.
3. Stir well for 30 minutes
4. Passing steam through the reactor jacket and heating the reaction mass to 75-80 ° C. for 1 hour under constant stirring.
5. Cooling the reaction mass to room temperature by recovering steam from the jacket.
6. The process of reducing the load in the stainless steel container with purified reaction mass
7. Hold the reaction mass at room temperature for 10-12 hours.
8. Tilting the top layer and collecting the bottom sediment mass.
9. Sift the sediment mass through a 5-micron mesh and collect the wet cake.
10. Adding DM water to the wet cake and bringing it to slurry.
11. Sieving through 5-micron mesh to remove tannin from product.
12. The process of washing with water more than twice.
13. In the process of drying the wet cake at 75-80 ° C. under reduced pressure and grinding it (Extract-C); the product is part of product #III.
14. Combine and load all three types of washings into the reactor.
15. Concentrating the material to a paste of about 20-25% total solids; (This water extract is added into Extract A of Process A.1, which is the product # 1 Part).

[Process B1: Extraction of outer skin with organic solvent]

[0108] Method B: In Method-B, the skin is extracted first with an organic solvent and then with water, as depicted in Figure 5).
1. Loading a known amount of dried and purified mangosteen skin into a suitable extractor.
2. Loading 6 volumes of about 80% alcohol.
3. Initiating heating of the reactor (extractor) by passing steam through the outer jacket.
4. Heating to 65 ° C-75 ° C and maintaining the temperature at reflux conditions of the extraction solvent and continuing under circulation for up to 2 hours.
5. Stopping heat input after 2 hours and cooling to room temperature.
6. Sifting the alcohol extract into a purified stainless steel container (solvent extract # 1).
7. Loading 4 volumes of alcohol into the reactor
8. Initiating heating of the reactor by passing steam through the outer jacket.
9. Heating to reflux temperature and continuing reflux under circulation for up to 2 hours.
10. Stop heat input after 2 hours and cool to room temperature.
11. Sieving the extract into a purified stainless steel container (solvent extract # 2).
12. Repeat steps 7 to 11 and collect the extract (solvent extract # 3).
13. Combining all three solvent extracts and loading it in a suitable reactor.
14. Evaporating the solvent from the extract and concentrating it to a semi-solid paste containing 40-45% total solids.
15. Holding the paste for about 10 hours.
16. Screening the paste through a 5-micron filter.
17. In the process of drying the wet cake at 75-80 ° C. under reduced pressure and crushing it (extract-B), extract #B of process # A.2 and extract of process # B.1 -B in combination, and this product is part of product #II (product- # I may be added into product #II to give the finished product II Equilibrium content of γ-mangostin, flavonoids and tannins as described in Table 1A). This final product is a light brown powder and its chemical composition is as follows:

18. The step of adding the sieving product to Extract-A of Process A.1, which is a water-soluble product and is the step included in Product-I.

[Process B.2: Extraction of used materials with water]

[0109] Process B.2 is drawn in Figure 6 and is operated as follows:
1. The process of loading a known amount of dry use from Process B.1 into a suitable extractor.
2. The process of loading 6 volumes of DM water.
3. Initiating heating of the extractor by passing steam through the outer jacket.
4. Heating to 85 ° C and maintaining the temperature under circulation for up to 2 hours.
5. Stopping heat input after 2 hours and cooling to room temperature.
6. Sifting the water extract into a purified stainless steel container (water extract # 1).
7. Loading 4 volumes of DM water into the extractor
8. Initiating heating of the extractor by passing steam through the outer jacket.
9. Heating to 85 ° C and maintaining the temperature under circulation for up to 2 hours.
10. Stop heat input after 2 hours and cool to room temperature.
11. Screening the water extract into a purified stainless steel container (water extract # 2).
12. Repeat steps 7 to 11 and collect the extract (water extract # 3).
13. Combining all three water extracts and loading them into a suitable reactor.
14. Distilling off water in the extract and concentrating to 20-25% total solids (TS).
15. Adding this extract into the water extract-A of process A.1, where it is part of product #I.

[Process B.3: Enrichment of extracts containing 20% γ-mangosteen to> 40%]

[0110] In Process B.3 (Figure 7), the wet cake obtained during Process # B.1 is further washed with water.
1. Loading a known amount of an extract containing 20% γ-mangostin into a suitable reactor.
2. Adding 8 volumes of DM water into the reactor.
3. Stir well for 30 minutes
4. Passing steam through the reactor jacket and heating the reaction mass to 75-80 ° C. for 1 hour under constant stirring.
5. Cooling the reaction mass to room temperature by recovering steam from the jacket.
6. Process to reduce the load in a stainless steel container with purified reaction mass
7. Hold the reaction mass at room temperature for 10-12 hours.
8. Tilting the top layer and collecting the bottom sediment mass.
9. Sifting the deposited mass through a 5-micron filter and collecting the wet cake.
10. Adding DM water into the wet cake and making it into a slurry.
11. Sifting through a 5-micron mesh to remove tannin from the product.
12. The process of washing with water more than twice.
13. Dry the wet cake at 75-80 ° C. under reduced pressure and grind it (Extract-C). Combine both Extract A from Process A.4 and Extract B from Process B.3 and use this product for production of Product #III (Product-I and / or Product- II may be added to product III to equilibrate the contents of γ-mangostin, flavonoids and tannins to give the finished product III as described in Table 1A). The chemical composition of the product is as follows:

14. Combining and loading all three types of washings and screened top layers into the reactor.
15. Concentrate the combined washings to a paste of 20-25% total solids.

  [0111] This is added into Extract-A, which is a part of Product #I. Extract-A (consisting of the water-soluble portion of all the different extracts) is spray dried. The variables for spray drying are as follows: a) Inlet temperature: 250 ° C, b) Outlet temperature: 108 ° C and c) Chamber pressure: -5 (mm of water column).

  [0112] The different extracts produced from the above methods A and B are combined in such a manner to obtain three desired products, namely products #I, II and III. A summary of the treatment for product I, 1% mangosteen is provided in FIG. 8; and a summary of the treatment for 20% mangosteen is provided in FIG. A summary of treatment for 40% mangosteen is provided in FIG. 10; details of treatment options for 40% mangosteen are provided in FIG. 11-13. The chemical and physical variables of these three examples as products I, II and III identified herein are shown in the following table:

[0113] Two different methods are provided to develop mangosteen extracts containing 40% mangosteen. Method 1 (FIG. 11) involves extracting the outer skin with DM water and then extracting the used product with an organic solvent. Method 2 involves extracting the outer skin directly with an organic solvent (FIG. 12) and then washing the concentrated extract with DM water (FIG. 13).

[Method 1 for 40% mangosteen (see Figure 11)]

1. This is a process in which a small piece of mangosteen skin is extracted with DM water (see: Treatment # 1), and then the remaining water is completely drained from the use. The remaining moist mangosteen skin pieces are known as mangosteen use.
2. The process of loading a known amount of Mangosteen use into a suitable extractor.
3. Loading 6 volumes of about 90% organic solvent, ie alcohol.
4. Initiating heating in the reactor (extractor) by passing steam through the outer jacket.
5. Heating to 65 ° C-75 ° C and maintaining the temperature at the reflux conditions of the extraction solvent and continuing for up to 2 hours.
6. Stop heat input after 2 hours and cool down to room temperature.
7. A step of sieving the alcohol (organic solvent) extract into a well-purified stainless steel container (solvent extract # 1).
8. Loading 4 volumes of 80% alcohol into the extractor
9. Initiating the heating of the reactor by passing steam through the outer jacket.
10. Heating to reflux temperature and continuing to reflux for 2 hours.
11. Stop heating after 2 hours and cool to room temperature.
12. Sieving the extract into a well-purified stainless steel container (solvent extract # 2).
13. Repeat steps 7 to 11 and collect the extract (solvent extract # 3).
14. Combine and collect all three solvent extracts in a suitable reactor.
15. Evaporate the solvent from the extract and concentrate to a semi-solid paste containing 40-45% total solids (TS). The chemical composition of the concentrated extract is as follows:

  16. Holding the concentrated paste for deposition for 10-12 hours at room temperature. After deposition, the paste is divided into upper and lower layers. Both layers are separated and analyzed.

17. Separating the bottom layer and sieving it through a 5-micron filter.
18. adding a minimum amount of water and bringing it to slurry;
19. Sifting through a 5-micron filter and suck dry the wet cake.
20. Drying the wet cake at 80 ° C. under constant vacuum. The final product is a light brown powder and has the following chemical composition:

[0114] A semi-solid product (TDS 20-25%) obtained from processing for mangosteen containing 20% γ-mangosteen is also enriched in extracts containing 40% and up to γ-mangosteen Can be used for For further enrichment of γ-mangosteen, approximately 20% to 40% and above is achieved by two different treatments.

[Method 2 treatment # 1 for 40% mangosteen (see Figure 12)]

1. Loading a known amount of an extract containing approximately 20% γ-mangostin into a suitable reactor.
2. Adding 5 volumes of DM water into the reactor.
3. Stir well for 30 minutes
4. Prepare 50 L of 5% potassium hydroxide (KOH) by dissolving 2.5 kg KOH in 50 L DM water.
5. Slowly adding 5% KOH solution to the reaction mass under constant agitation to bring the pH from 8.0 to 8.2.
6. Heating the reaction mass to 55-60 ° C under constant stirring for 1 hour.
7. Cooling the reaction mass to room temperature.
8. Check pH and maintain pH 8.0-8.2 by adding 5% KOH.
9. Heating the reaction mass to 55-60 ° C under constant stirring for 0.5 hours.
10. Cooling the reaction mass to room temperature.
11. The process of reducing the load in the container in which the reaction mass has been purified.
12. Keeping the reaction mass at room temperature for 10-12 hours,
13. Tilting the top layer and collecting the bottom sediment mass.
14. Sifting the sediment mass through a 5 micron filter and collecting the wet cake.
15. Adding a minimum amount of DM water to the wet cake and bringing it to slurry.
16. Screening through a 5-micron mesh to remove excess KOH from the product.
17. Drying the wet cake at 75 ° C. under reduced pressure.

1. Loading a known amount of an extract containing 20% γ-mangostin into a suitable reactor.
2. Adding 8 volumes of DM water into the reactor.
3. Stir well for 30 minutes
4. Passing steam through the reactor jacket and heating the reaction mass to 75-80 ° C. with constant stirring for 1 hour.
5. Cooling the reaction mass to room temperature by recovering steam from the jacket.
6. Passing the brine solution through the jacket and cooling the reaction mass to -5 ° C for 5 hours.
7. Allowing the reaction mass to return to room temperature.
8. The process of reducing the load in the stainless steel container with purified reaction mass
9. Holding the reaction mass at room temperature for 10-12 hours.
10. Tilting the top layer and collecting the bottom sediment mass.
11. Sift the sediment mass through a 5-micron mesh and collect the wet cake.
12. Adding DM water to the wet cake and making it into a slurry.
13. Sifting through the 5-micron mesh to remove tannin from the product.
14. The process of repeating washing with water more than twice.
15. Drying the wet cake at 75 ° C. under reduced pressure and grinding it. The chemical composition of the extract is as follows:

16. Combining all three types of washings with a screened top layer and loading into the reactor.
17. Concentrate it to 20-25% TS paste
18. The process of spray-drying the product.

[0115] This water product is water soluble and is used as a diluent for Garcinia rind extract to prepare a formulation containing the desired amount of γ-mangosteen. The variables for spray drying and spray drying are as follows: a) Inlet temperature: 250 ° C, b) Outlet temperature: 108 ° C and c) Chamber pressure: -5.

[In vitro and bench level surveys]

[0116] The safety and efficacy of the mangosteen compositions described herein are demonstrated by the following examples, which are listed for illustrative purposes only and for prophylactic or therapeutic use It is not limited to examples. A therapeutic composition of a mangosteen pericarp mixture (Xanomax® ⁽ Xanomax ™) 10%) was prepared according to the embodiments described herein, and safety in vitro cytotoxicity testing and anti-antibody -Used as an article in a bench level investigation of oxidant throughput. In addition, examples of various product forms of mangosteen compositions are described, and examples of their beneficial effects on human health are provided.

[Toxicity Survey 1]

[0117] The purpose of this study was to evaluate mangosteen extracts for their level of cytotoxicity in mammalian systems. Thus, a serially diluted 10% mangosteen peel test article that is about cytotoxicity to mammalian cells in culture (L-929 mouse fibroblasts, American Type Culture Collection (American Type Culture Collection)). From collection: CCL-1). The test article is an original 10% mangosteen preparation), in a suitable volume of cell culture medium (Earle's Minimal Essential Medium, E-MEM), 24-25 in a sterile container. Incubation (incubation) at 37 ± 1 ° C. until At the end of the extraction period, the extract was tilted from the test article. Eight (8) dilutions of the series of extracts were prepared in a two-fold dilution sequence in culture medium. After the dilution was prepared, the maintenance culture medium was removed from the test culture well and replaced with 1 mL of the test dilution of the article. Cytotoxic positive control medium (100 μmol CdCl ₂ ), dilution of test article extract, and control extract were added simultaneously in triplicate wells to the culture plate. Cell culture plates were incubated for 72 hours at 37 ± 1 ° C. in air with 5 ± 1% CO ₂ in a humid atmosphere. Cultures were evaluated for cytotoxic effects by microscopic examination at 24, 48, and 72 ± 4 hours incubation, and the results were scored and recorded.

  [0118] The final assessment of the validity of the assay and test article results was based on the following criteria and scientific judgment. At the time of lysis scoring, each culture was rated for the amount of lysis indicated by the negative control. A negative control was considered “0” if the cells displayed at least 70% survival. Cell viability less than 70% and / or degeneration greater than 10% displayed in the negative control dish (dish) is considered an indication of a problem inherent to the cell or culture technique, and therefore the test results can be used for any analysis. Not used. Only valid assays, those with suitable positive and negative control results were included in the analysis. The positive control displayed a moderate to severe cytotoxic response, resulting in a score of “3” or “4”.

  [0119] The test article was submitted as a powder and maintained at room temperature. The stock solution was prepared by mixing 4.2 g test article with 21 mL E-MEM + 5% fetal bovine serum (FBS). The mixture was incubated at 37 ± 1 ° C. for 24-25 hours. After incubation, the mixture was separated into two layers. The visually apparent particle-free layer was removed from the tube and transferred to the centrifuge tube. The liquid was then centrifuged at 3000 rpm for 10 minutes. The resulting supernatant was then used for testing. Lower doses were prepared from this stock by dilution with E-MEM + 5% FBS just prior to use. An aliquot of the stock solution was taken for pH measurement.

  [0120] Criteria for assessing cytotoxicity include morphological changes in cells, which include granulation, crenation, rounding, lysis or exfoliation. It is like loss of viable cells from a monolayer due to (detachment). The validity of the test requires that the negative control culture maintain a healthy and normal appearance for the duration of the test. The degree of toxicity is scored according to the mechanism in Table 2:

  [0121] After the initial incubation of the storage mixture, the medium is found to be dark brown in color, it contains a high level of flocculent powder, and the pH of the mixture is It was 4.03. During the initial two scoring periods, the top two doses could not be scored due to debris levels. In order to visualize the cells during the final scoring period, neat dosed wells are washed with phosphate buffered saline. did. This allowed for single layer visualization and subsequent scoring. As shown in Table 3, it was noted that the two dose levels (1: 4 and 1: 8 dilutions) gently affect the cells. However, at a 1:16 dilution, the cells looked morphologically abnormal, consistent with complete cell death.

[0122] Test article, Xanomax ^(R) 10% are scored "4" at 72 ± 4 hours, and is considered toxic at that level under the conditions of this test. However, the levels of the four more concentrated doses did not induce the type of morphological change associated with significant toxicity. At the 1:32 dose, the test article did not induce substantial morphological changes. As such, the test article is considered to have passed the assay at a dilution of 1:32. At higher levels of dilution, there is clearly no evidence of cytotoxicity.
[Toxicity Survey 2]

[0123] The purpose of this study was to evaluate serially diluted extracts of 40% mangosteen peel test articles in culture for cytotoxicity against mammalian cells. The test article was incubated in a sterilized container in a suitable volume of E-MEM for 24-25 hours at 37 ± 1 ° C. After steps were taken to create a clear supernatant, a series of eight (8) dilutions of the extract were prepared in fold dilutions in E-MEM. After the dilutions were prepared, the maintenance culture medium was removed from the test culture wells and replaced in triplicate wells with 1 mL of dilution of the test medium. Positive control medium, test article extract, and control extract were added simultaneously to triplicate wells in triplicate wells. Plates were incubated for 72 hours at 37 ± 1 ° C. in air with 5 ± 1% CO ₂ in a humid atmosphere. Cultures were evaluated for cytotoxic effects by microscopic examination at 24, 48, and 72 ± 4 hours incubation, and the results were scored and recorded. After 24 hours of extraction, the liquid was transferred to a 50 mL conical tube and centrifuged for 10 minutes at 3000 rpm. The granules (pellet) created by separation were discarded and the resulting supernatant was clear, had a light brown color and a pH of 7.5.

  [0124] Criteria for assessing cytotoxicity include morphological changes in cells, which are survival from a monolayer by granulation, serrated, or lipization, lysis or detachment. It's like a loss of cells. The validity of the test requires that the negative control culture maintain a healthy and normal appearance for the duration of the test. The degree of toxicity is scored as in Table 1 (Table 2) above:

  [0125] The results of the assay are presented in Table 3 (Table 4). By microscopic evaluation, a significant amount of test article debris was noted in all wells treated with neat extract. The final 3-day evaluation was performed by two scientists. While cells treated with neat extract appear to be more rounded and some circular sawtooth formation may be shown compared to the negative control, they are alive and extensive lysis is not noted It was. Cells appeared dead in wells treated with a 1: 4 dilution (completely rounded and circular serrated) and cells appeared attached.

[0126] The test article, Xanomax® ⁽ 40%), was scored “4” at 24 and 48 ± 4 hours and “2” at the neat concentration at 72 ± 4 hours, and under the conditions of this test At this dose level is considered non-toxic. At 1: 2 dilution, the test article is scored “2” at the observation period of 24, 48 and 72 hours, while at the 1: 4 dose level it is at the observation period of 24, 48 and 72 hours. Induced a score of “4”. Thus, the 1: 2 dose level was thought to induce a non-toxic response, while the 1: 4 dose was found to be toxic. All other dose levels are scored to “0” and considered non-toxic under the conditions of this study.

[ORAC and COX analysis]

  [0127] Analysis of oxygen radical absorption capacity (ORAC) is a reliable and recognized standard test of the capacity of natural product antioxidants. Even more particularly, this assay provides a measure of the ability of antioxidants to scavenge peroxyl radicals, which is one of the most common reactive oxygen species (ROS) found in the body. ORAC / hydro reflects the processing capacity of water-soluble antioxidants, and ORAC / lipo is the processing capacity of fat-soluble antioxidants. ORAC / total is the sum of ORAC / hydro and ORAC / lipo: Trolox, water-soluble vitamin E analog (analog) is used as a calibration standard, and ORAC results are measured in micrograms per gram Expressed as moles Trolox equivalent (TE). Caffeic acid is used as a calibration standard and the HORAC (ORAC test specific for hydroxyl radical) results are expressed as μmol caffeic acid equivalent (CAE) per gram. Trolox is used as the calibration standard and the NORAC results are expressed as μmol Torolox equivalents (TE) per gram.

  [0128] The activity of cyclooxygenase (COX) was measured at 37 ° C by monitoring oxygen consumption using an Oxytherm Electrode Unit by Hansatech. IC50 is equal to the concentration of the sample that inhibits 50% of the enzyme activity under assay conditions. Selective inhibitors of COX-2 reduce pain and inflammation.

  [0129] Data from these various tests are of a representative sample of inventive compositions with 40% mangosteen, as performed by an independent laboratory, and are reported in Table 5. A comparison of representative samples of 1%, 10%, 20%, and 40% mangosteen compositions is detailed in Table 6. These in vitro test data demonstrate highly effective free radical scavenging activity with inventive mangosteen compositions for peroxyl, hydroxyl, peroxynitrite, and superoxide anion radicals.

[発明の等価物]

[Equivalents of the invention]

  [0130] Although numerous preferred embodiments of the invention and variations thereof have been described in detail, other modifications and methods using the disclosed therapeutic combinations will be apparent to those skilled in the art. Accordingly, it should be understood that various applications, modifications, and substitutions may be made from equivalents without departing from the spirit of the scope of the invention and the claims. Various terms and conventions have been used in the description to convey an understanding of the present invention. It will be understood that the corresponding description of these various terms applies to the usual linguistic or grammatical variations of these various terms. Also, although some compounds have been identified by trade names, these names are provided as examples of the present generation, and the present invention is not limited by such literal scope, particularly when the compounds are described in chemical terms. Understood. While the written description provides an interpretation of the available data in the biochemical theory and description of the invention, it should be understood that such theory and interpretation do not limit or limit the scope of the claims. Further, while not being understood, the invention is not limited to the specific examples for purposes of illustration described herein, the equivalent claims in which each element is entitled to the appended claims are not limited. It should be understood that the provisions should be made only by fair reading, including the scope.

It is a flowchart (flowchart) about process A.1 and a water extraction process. It is a flowchart about process A.2, alcohol extraction process. It is a flowchart about process A.3 and an additional water extraction process. It is a flowchart about process A.4 and enrichment process. Fig. 11 is a flowchart for treatment B.1, an extraction treatment with an organic solvent. It is a flowchart about process B.2 and a water extraction process. It is a flowchart about process B.3 and enrichment process. 2 is a flow diagram for a 1% mangosteen extract treatment. Figure 2 is a flow chart for a 20% mangosteen extract treatment. FIG. 5 is a flow chart for 40% mangosteen extract processing. 2 is a flow diagram for 40% mangosteen extract treatment, Method 1. 2 is a flow diagram for 40% mangosteen extract treatment, Method 2, Treatment 1. 2 is a flow diagram for 40% mangosteen extract treatment, Method 2, Treatment 2.

Claims (46)

  A composition comprising a concentrated extract of mangosteen peel, wherein the extract comprises xanthone at a concentration between about 0.1% and about 80% of the total weight of the composition, and the composition comprises tannin, xanthone A composition comprising a concentration that is adjusted independently of the concentration of.   2. The composition of claim 1, wherein the extract is present at a concentration between about 0.3% and about 60% of the total weight of the composition.   2. The composition of claim 1, wherein the extract is present at a concentration between about 1.0% and about 40% of the total weight of the composition.   2. The composition of claim 1, wherein the extract is present at a concentration of about 1% of the total weight of the composition.   2. The composition of claim 1, wherein the extract is present at a concentration of about 10% of the total weight of the composition.   2. The composition of claim 1, wherein the extract is present at a concentration of about 20% of the total weight of the composition.   2. The composition of claim 1, wherein the extract is present at a concentration of about 40% of the total weight of the composition.   2. The composition of claim 1, wherein the composition is a therapeutic agent sufficient for the prevention or treatment of disease.   9. The composition of claim 8, wherein the composition is a therapeutic agent sufficient for the prevention or treatment of human disease.   9. The composition of claim 8, wherein the composition is sufficient for the prevention or treatment of skin diseases.   11. The composition of claim 10, wherein the skin condition is associated with exposure to ultraviolet radiation.   The skin disease is selected from the group consisting of sunburn, photosensitivity, skin-localized allergy, immunosuppression, premature aging, psoriasis, cancerous damage, precancerous damage, bacterial infection, viral infection, fungal infection, and rash 11. The composition of claim 10, wherein the composition is at least one.   13. The composition according to claim 12, wherein the precancerous injury or cancerous injury is one selected from the group consisting of actinic keratosis, basal cell carcinoma, squamous cell carcinoma, and malignant melanoma.   11. The composition of claim 10, wherein the skin disease is polymorphic photorash.   9. The composition of claim 8, wherein the composition is sufficient for tissue bioprotection, wherein such bioprotection prevents or treats a condition selected from the group consisting of allergy, inflammation, and planned death.   9. The composition of claim 8, wherein the composition is an antioxidant sufficient for the treatment of a disease resulting from exposure to reactive oxygen species.   17. The composition of claim 16, wherein the disease resulting from exposure to reactive oxygen species is a skin disease.   A composition comprising a concentrated extract of mangosteen peel, the extract comprising at least one xanthone selected from the group consisting of α-mangosteen, β-mangosteen, and γ-mangosteen, and the composition A composition comprising tannin at a concentration that is regulated independently of the concentration of xanthone.   Further, (1) carbaxanthone, (2) demethylcarbaxanthone, (3) 6-deoxy-γ-mangosteen, (4) 1-isomangosteen, (5) 3-isomangosteen, (6) 1-isomangosteen Hydrate, (7) 3-Mangosteen hydrate, (8) Gartanine, (9) 8-Deoxygartanine, (10) Garcinone A, (11) Garcinone B, (12) Garcinone C, (13) Garcinone D, (14) Garcinone E, (15) Mangostanol (prenylxanthone), (16) Mangostanol (polyoxygenated xanthone), (17) 6-deoxy-γ-mangostin, (18) Mangostinone, (19) 1 , 5-dihydroxy-2- (3-methylbut-2-enyl) -3-methoxyxanthone, (20) 1,7-dihydroxy-2- (3-methylbut-2-enyl) -3-methoxyxanthone, (21 ) 1,5-dihydroxy-3-methoxy-2- (3-methylbut-2-enyl) xanthone, (22) 1,7-dihydroxy-3-methoxy-2- (3-methylbut-2-enyl) xanthate (23) 5,9-dihydroxy-2,2-dimethyl-8-methoxy-7- (3-methylbut-2-enyl) -2H, 6H-pyrano [3,2b] xanthen-6-one, (24 ) 2- (γ, γ-dimethylallyl) -1,7-dihydroxy-3-methoxyxanthone, (25) 2,7-di- (3-methylbut-2-enyl) -1,3,8-trihydroxy -4-methylxanthone, (26) 2,8-di- (3-methylbut-2-enyl) -7-carboxy-1,3-dihydroxyxanthone, (27) normangostin (ν-mangostin), (28) 1,5,8-trihydroxy-3-methoxy-2- (3-methyl-2-butenyl) xanthone, (29) 1,7-dihydroxy-2-isoprenyl-3-methoxyxanthone, (30) xanthone I, (31) BR-xanthone A, (32) BR-xanthone B (2,4,5-trihydroxy-1-methoxyxanthone), (33) garcinone B, (34) mangostanol, (35) mangostenol, (36) Mangostenone A, (37) Mangostenone B, (38) Tobophilin, and (39) Trapezifo Comprising at least one xanthone is selected from the group consisting of xanthone composition of claim 18.   Further, one or more kinds of compounds in the group consisting of (-)-epicatechin, procyanidin A-2, procyanidin B-2, garcinone A, garcinone B, garcinone C, garcinone D, garcinone E, and mcurlin 20. The composition of claim 18 or 19, comprising.   A composition comprising at least one xanthone selected from the group consisting of α-mangostin, β-mangosteen, and γ-mangostin, and the composition is adjusted to tannin independently of the concentration of xanthone A composition comprising at a concentration.   Further, (1) carbaxanthone, (2) demethylcarbaxanthone, (3) 6-deoxy-γ-mangosteen, (4) 1-isomangosteen, (5) 3-isomangosteen, (6) 1-isomangosteen Hydrate, (7) 3-Mangosteen hydrate, (8) Gartanine, (9) 8-Deoxygartanine, (10) Garcinone A, (11) Garcinone B, (12) Garcinone C, (13) Garcinone D, (14) Garcinone E, (15) Mangostanol (prenylxanthone), (16) Mangostanol (polyoxygenated xanthone), (17) 6-deoxy-γ-mangostin, (18) Mangostinone, (19) 1 , 5-Dihydroxy-2- (3-methylbut-2-enyl-3-methoxyxanthone, (20) 1,7-dihydroxy-2- (3-methylbut-2-enyl) -3-methoxyxanthone (21) 1 , 5-dihydroxy-3-methoxy-2- (3-methylbut-2-enyl) xanthone, (22) 1,7-dihydroxy-3-methoxy-2- (3-methylbut-2-enyl) xanthone, (23) 5,9-dihydroxy-2,2-dimethyl-8-methoxy-7- (3-methylbut-2-enyl) -2H, 6H-pyrano [3,2b] xanthen-6-one, (24) 2- (γ, γ-dimethylallyl) -1,7-dihydroxy-3-methoxyxanthone, (25) 2,7-di- (3-methylbut-2-enyl) -1,3,8-trihydroxy- 4-methylxanthone, (26) 2,8-di- (3-methylbut-2-enyl) -7-carboxy-1,3-dihydroxyxanthone, (27) normangostin (ν-mangostin), (28) 1 , 5,8-trihydroxy-3-methoxy-2- (3-methyl-2-butenyl) xanthone, (29) 1,7-dihydroxy-2-isoprenyl-3-methoxyxanthone, (30) xanthone I, ( 31) BR-xanthone A, (32) BR-xanthone B (2,4,5-trihydroxy-1-methoxyxanthone), (33) garcinone B, (34) mangostanol, (35) mangostenol, ( 36) Mangostenone A, (37) Mangostenone B, (38) Tobophilin, and (39) Trapezforiki 23. The composition of claim 21, comprising at least one xanthone selected from the group consisting of Sandton.   Further, one or more kinds of compounds in the group consisting of (-)-epicatechin, procyanidin A-2, procyanidin B-2, garcinone A, garcinone B, garcinone C, garcinone D, garcinone E, and mcurlin 23. The composition of claim 21 or 22, comprising:   2. The composition of claim 1, wherein the composition is a nutritional supplement and is sufficient to provide a health benefit.   25. The composition of claim 24, wherein the nutritional supplement is incorporated into a form selected from the group consisting of food and drink.   9. The composition of claim 8, further comprising at least one second therapeutic agent, forming a combined therapeutic entity, wherein the entity is sufficient to prevent or treat the disease.   27. The combination therapeutic entity of claim 26, which is sufficient to prevent or treat a skin condition.   28. The composition of claim 27, wherein the skin disease is abnormal skin differentiation, proliferation, or pigmentation, bacterial infection, parasitic infection, fungal infection, inflammation, pain or irritation from any cause A composition comprising one or more types of conditions selected from the group consisting of pruritus, viral drugs, epidermis stripping, UV (ultraviolet) radiation damage, seborrhea, dandruff, and acne.   28. The composition of claim 27, wherein the at least one second agent is a regulator of skin differentiation and / or proliferation and / or pigmentation, an antibacterial agent, an antiparasitic agent, an antibacterial agent, Group consisting of steroidal anti-inflammatory drugs, anesthetics, antipruritic drugs, antiviral drugs, epidermis stripping drugs, other anti-oxidants, antiseborrheic drugs, antidandruff drugs, and anti-acne drugs The composition selected from.   A method for treating skin diseases caused by exposure to sunlight, comprising the step of managing a composition comprising a concentrated extract of mangosteen peel, wherein the extract is about 0.1% of the total weight of the composition From about 80% to about 80%, and such compositions have independently adjusted tannin concentrations.   32. The method of claim 30, wherein the extract is particularly at a concentration from about 0.3% to about 60% of the total weight of the composition.   32. The method of claim 30, wherein the extract is even more particularly at a concentration from about 0.1% to about 40% of the total weight of the composition. Treatment (A.1), wherein the hull is water-extracted and the hull used thereby is then extracted with an organic solvent and again with water:
1. loading a volume of mangosteen skin pieces into an extractor,
2. Loading about 6 volumes of water into the extractor,
3. heating the extractor to about 85 ° C and maintaining the temperature for up to about 2 hours;
4. Cooling the extractor to room temperature,
5. Sifting the water extract into a container to give water extract # 1,
6. The process of loading 4 volumes of water into the extractor,
7. heating the reactor (extractor) to about 85 ° C. and maintaining that temperature for up to about 2 hours;
8. Cooling the reactor to room temperature,
9. Sifting the water extract into a container to yield water extract # 2, and
10. Combine both water extracts # 1 and # 2 and concentrate to about 20-25% total solids, resulting in extract-a, which is part of product #I Including, processing. Process (A.2), wherein the shell of the use of process A.1 is extracted with an organic solvent and again with water:
1. loading one volume of re-dried material with mangosteen hull from process A.1 into the extractor;
2. A process of loading about 6 volumes of about 80% alcohol into the reactor (extractor),
3. heating the reactor to 65 ° C-75 ° C and maintaining the temperature at the reflux conditions of the extraction solvent for up to about 2 hours;
4. cooling the reactor to room temperature,
5. Sifting the alcohol extract into a container to yield solvent extract # 1;
6. loading about 4 volumes of alcohol into the reactor,
7. heating the reactor to reflux temperature and continuing the reflux for up to about 2 hours;
8. Cooling the reactor to room temperature,
9. Sifting the extract into a container to yield solvent extract # 2,
10. Repeat steps 6 to 9 and collect the extract (solvent extract # 3),
11. Combine and load all three solvent extracts into the reactor,
12. evaporating the solvent from the extract and concentrating to a semi-solid paste containing about 40-45% total solids;
13. Holding the semi-solid paste for 8-10 hours settling at room temperature,
14. The process of separating the paste into two parts, upper and lower layers, after settling,
15. separating the bottom layer and sieving through a 5-micron (μm) filter;
16. Mixing the residue after sieving the lower and upper layers to give a wet cake,
17. drying the wet cake at about 75-80 ° C. under constant vacuum and crushing it to give extract-b (this product is part of product #ii), and
18. Concentrate the screened top layer to a paste of about 20-25% total solids (this product is highly water soluble and added into extract-a, which is (It is a part of object #I)
Including, processing. Treatment (A.3), the solvent-extracted material is once again extracted with water to obtain other tannins:
1. a process of loading a volume of dry use into the extractor,
2. Loading about 4 volumes of water into the reactor (extractor),
3. heating the reactor to 85 ° C and maintaining that temperature for up to 2 hours;
4. cooling the reactor to room temperature,
5. Sifting the water extract into a container to give water extract # 1,
6. The process of loading about 4 volumes of water into the reactor,
7. heating the reactor to 85 ° C. and maintaining the temperature for up to about 2 hours;
8. Cooling the reactor to room temperature,
9. Sifting the water extract into a container to provide water extract # 2, and
10. Combine both extracts and concentrate to about 20-25% total solids (add this aqueous extract into Extract A of Process A.1, which is the product #I (One part)
Including, processing. Treatment (A.4), where the wet cake of Extract A-b from Treatment A.2 is treated again to obtain an extract containing at least 40% mangosteen, which is part of product #III :
1. loading a reactor with 1 volume of an extract (wet cake) containing 20% mangosteen,
2. adding 8 volumes of water into the reactor,
3. Stir well for about 30 minutes,
4. heating the reaction mass to 75-80 ° C under constant stirring for 1 hour;
5. cooling the reaction mass to room temperature,
6. Reducing the load of the reaction mass in the container,
7. holding the reaction mass at room temperature for about 10-12 hours;
8. Tilting the top layer and collecting the bottom sediment mass,
9. screening the sediment mass and collecting the wet cake;
10. adding water to the wet cake and making it a slurry;
11. sieving to remove tannin from the product,
12. The process of repeating washing with water more than twice,
13. Dry the wet cake at about 75-80 ° C. under reduced pressure and grind it (extract-c); a process in which this product is part of product #III;
14. Combine and load all three types of washings into the reactor, and
15. Concentrate the material to a paste of 20-25% total solids; (Add this water extract into Extract-a of Process A.1, which is part of product #I )
Including, processing. Treatment (method B.1), in which the hull is first extracted with an organic solvent and then with water:
1. The process of loading a volume with a dried mangosteen rind into the extractor,
2. Loading 6 volumes of about 80% alcohol,
3. heating the reactor (extractor) to about 65 ° C-75 ° C and maintaining the temperature at the reflux conditions of the extraction solvent and continuing for up to 2 hours;
4. cooling the reactor to room temperature,
5. Sifting the alcohol extract into a container (solvent extract # 1),
6. loading about 4 volumes of alcohol into the reactor,
7. heating the reactor to reflux temperature and continuing the reflux for up to about 2 hours;
8. Cooling the reactor to room temperature,
9. Screening the extract into a container, (solvent extract # 2),
10. Repeat steps 5 to 9 and collect the extract (solvent extract # 3),
11. Combining all three solvent extracts and loading it in a suitable reactor,
12. evaporating the solvent from the extract and concentrating it to a semi-solid paste containing about 40-45% total solids;
13. Hold the paste for about 10 hours,
14. The process of sieving the paste,
15. Dry the wet cake at about 75-80 ° C. under reduced pressure and grind it (extract-b), extract of process # a, 2-b and extract of process # b, 1- b), and this product is part of product #II (product-I may be added to product II, mangosteen, flavonoids and tannins to give the finished product II The content of
16. A process comprising adding a sieve to Extract-a of Process A.1, which is a water-soluble product and includes the process included in Product-I. Process (B.2), where the outer skin of the use of process B.1 is extracted with water:
1. loading one volume of dry use from treatment B.1 into the extractor;
2. Loading about 6 volumes of water into the extractor,
3. heating the extractor to about 85 ° C and maintaining the temperature for up to about 2 hours;
4. The process of cooling the reactor (extractor) to room temperature,
5. Screening the water extract into the container, (water extract # 1),
6. The process of loading 4 volumes of water into the extractor,
7. heating the extractor to 85 ° C and maintaining the temperature for up to about 2 hours;
8. Cooling the reactor to room temperature,
9. Sifting the water extract into a container to give water extract # 2,
10. Repeat steps 6-9 and collect the extract to give water extract # 3,
11. Combine and load all three water extracts into the reactor,
12. evaporating water in the extract and concentrating to about 20-25% total solids;
13. A process comprising adding this extract to the water extract-a of process A.1, comprising a part of product I. Process (B.3), to enrich (enrich) an extract containing 20% to 40% mangosteen, obtained during process # B.1 Wash further with water:
1. loading a volume of an extract containing 20% γ-mangostin into a suitable reactor,
2. adding 8 volumes of water into the reactor and stirring well for about 30 minutes,
3. heating the reaction mass to about 75-80 ° C. for 1 hour with constant stirring;
4. cooling the reaction mass to room temperature,
5. Reducing the load of reaction mass in the container,
6. holding the reaction mass at room temperature for about 10-12 hours;
7. Tilting the top layer and collecting the bottom sediment mass,
8. screening the sediment mass and collecting wet cake;
9. adding water to the wet cake and making it into a slurry;
10. screening the slurry to remove tannin from the product;
11. The process of repeating washing with water more than twice,
12. Dry the wet cake under reduced pressure at about 75-80 ° C. and grind it (extract-c), extract extracts from process a, 4-c and extract from process b, 3-c Combine both and use this product for the production of product #III, (Product-I and / or Product-II may be added to Product III and completed as described in Table 1. In order to give the product III, the content of γ-mangostin, flavonoids and tannins is equilibrated), the chemical composition of the product follows
13. Combine and load all three types of washings into the reactor, and
14. Processing comprising concentrating the combined washings to a paste of 20-25% total solids. Processing to derive a 40% mangosteen extract:
1. After a small piece of mangosteen rind is extracted with water (Ref: Treatment # 1), the remaining moist mangosteen rind piece is used by mangosteen in the process of draining any remaining water from the use. A process known as a thing,
2. loading a known amount of mangosteen use into a suitable extractor;
3. Loading 6 volumes of 90% organic solvent,
4. Initiating heating in the reactor (extractor) by passing steam through an external jacket,
5. heating to 65 ° C.-75 ° C. and maintaining the temperature at the reflux conditions of the extraction solvent and continuing for up to 2 hours;
6. Stop heat input after 2 hours and cool to room temperature,
7. Sifting the alcohol (organic solvent) extract into a well-purified stainless steel container, (solvent extract # 1),
8. The process of loading 4 volumes of alcohol into the extractor,
9. Initiating heating of the reactor by passing steam through an external jacket,
10. heating to reflux temperature and continuing reflux for up to 2 hours;
11. Heating off after 2 hours and cooling to room temperature,
12. Screening the extract into a well-purified stainless steel container, (solvent extract # 2),
13. Repeat steps 7 to 11 and collect the extract (solvent extract # 3),
14. combining all three solvent extracts and collecting it in a suitable reactor;
15. evaporating the solvent from the extract and concentrating to a semi-solid paste containing 40-45% total solids;
16. holding the concentrated paste for deposition for about 10-12 hours at room temperature;
17. dividing the paste into upper and lower layers, separating and analyzing both layers;
18. separating the lower layer and sieving it,
19. adding a minimum amount of water and making it into a slurry;
20. Sifting through a 5-micron filter and sucking the wet cake dry, and
21. Treatment comprising drying the wet cake at 80 ° C. under constant vacuum to yield the final product, a light brown powder. Processing (Method 2) for deriving 40% mangosteen extract:
1. loading a reactor with a volume of an extract containing approximately 20% mangosteen,
2. adding 5 volumes of water into the reactor,
3. Stir well for 30 minutes,
4. Slowly adding 5% KOH solution to the reaction mass under constant agitation to bring the pH from 8.0 to 8.2;
5. heating the reaction mass to 55-60 ° C under constant stirring for 1 hour,
6. cooling the reaction mass to room temperature,
7. Check pH and maintain pH 8.0 to 8.2 by addition of 5% KOH,
8. heating the reaction mass to 55-60 ° C under constant stirring for 0.5 hours,
9. cooling the reaction mass to room temperature;
10. Reducing the load of the reaction mass in the container,
11. Hold the reaction mass at room temperature for 10-12 hours,
12. Tilting the top layer and collecting the bottom sediment mass,
13. Sifting the sediment mass through a 5 micron filter and collecting the wet cake;
14. Adding a minimum amount of water to the wet cake to make it into a slurry;
15. Sifting the slurry to remove excess KOH from the product; and
16. Treatment comprising drying the wet cake at 75 ° C. under reduced pressure. Processing (Method # 2) to extract 40% mangosteen:
1. loading a volume of an extract containing 20% mangosteen in the reactor,
2. adding 8 volumes of water into the reactor,
3. Stir well for 30 minutes,
4. heating the reaction mass to 75-80 ° C under constant stirring for 1 hour;
5. Cooling the reaction mass to room temperature and then cooling (chilling) the reaction mass to −5 ° C. for 5 hours,
6. The step of returning the reaction mass to room temperature,
7. reducing the load of the reaction mass in the container and holding at room temperature for about 10-12 hours;
8. Tilting the top layer and collecting the bottom sediment mass,
9. screening the sediment mass and collecting the wet cake;
10. adding water to the wet cake and making it into a slurry;
11. screening the slurry to remove tannin from the product;
12. The process of repeating washing with water more than twice,
13. Drying the wet cake at 75 ° C. under reduced pressure and grinding it, combining all three washings and loading into the reactor,
14. Concentrating it to a paste of 20-25% total solids, and
15. Processing comprising the step of spray drying (spray-drying) the product. A method for preparing a concentrated extract of mangosteen peel;
Operating the process according to claim 33;
Operating the process according to claim 34;
Operating the process according to claim 35;
Operating a process according to claim 36;
Operating a process according to claim 37;
40. A method comprising: operating a process according to claim 38; and operating a process according to claim 39.   44. The method of claim 43, wherein the final product has a content of at least 1%, a flavonoid content of at least 5%, and a tannin of at least 15%.   44. The method of claim 43, wherein the final product has a content of at least 20%, a flavonoid content of at least 40%, and a tannin of at least 12%.   44. The method of claim 43, wherein the final product has a content of at least 40% and a flavonoid content of at least 95%.

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